The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanopart...The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanoparticles AT-R@CMSN exhibiting geometrical chiral structure were designed to improve the surface/interface roughness in nanoscale,and employed as the hosting system for insoluble drugs nimesulide(NMS)and ibuprofen(IBU).Once performing the delivery tasks,AT-R@CMSN with rigid skeleton protected the loaded drug and reduced the irritation of drug on gastrointestinal tract(GIT),while their porous structure deprived drug crystal and improved drug release.More importantly,AT-R@CMSN functioned as“antiskid tire”to produce higher friction on intestinal mucosa and substantively influencedmultiple biological processes,including“contact”,“adhesion”,“retention”,“permeation”and“uptake”,compared to the achiral S@MSN,thereby improving the oral adsorption effectiveness of such drug delivery systems.By engineering AT-R@CMSN to overcome the stability,solubility and permeability bottlenecks of drugs,orally administered NMS or IBU loaded AT-R@CMSN could achieve higher relative bioavailability(705.95%and 444.42%,respectively)and stronger anti-inflammation effect.In addition,AT-R@CMSN displayed favorable biocompatibility and biodegradability.Undoubtedly,the present finding helped to understand the oral adsorption process of nanocarriers,and provided novel insights into the rational design of nanocarriers.展开更多
BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment,...BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1 beta, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1 beta converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1 beta, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1 beta and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1 beta and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines, including IL-1 beta and IL-18. Our animal data may be applicable in clinical practice.展开更多
Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seven...Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin.Each treatment has six replicates of six pigs.After 14 days,6 pigs from each treatment were selected and the jejunal samples were collected.Results:Results showed that supplemental tributyrin increased(P<0.05)villus height and villus height:crypt depth of weaned pigs.Pigs fed tributyrin had greater(P<0.05)RNA/DNA and protein/DNA ratios than pigs on the control group.The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated(P<0.05)in pigs fed the tributyrin diet.Dietary tributyrin supplementation lowered(P<0.05)the malondialdehyde and hydrogen peroxide(H2O2)content in jejunum,enhanced(P<0.05)the mitochondrial function,as demonstrated by decreased(P<0.05)reactive oxygen species level and increased(P<0.05)mitochondrial membrane potential.Furthermore,tributyrin increased(P<0.05)mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions,including peroxisomal proliferator-activated receptor-γcoactivator-1α,mitochondrial transcription factor A,nuclear respiratory factor-1 in the jejunum.Supplementation with tributyrin elevated(P<0.05)the phosphorylation level of AMPK and inhibited(P<0.05)the phosphorylation level of mTOR in jejunum compared with the control group.Conclusions:These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth,extenuates oxidative stress,improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.展开更多
[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body's immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secret...[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body's immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secretory type immune globulin cell A were dynamic observed to research chicken immune organ growth with histology conventional slice technology and immunohistochemistry dye. 1 day age healthy roosters were divided into 3 groups: the group 3 was control group. 1% and 0.5% concentration of Chinese herbal medicine immunopotentiator drinking water were added in the group 1 and 2 in continuous 60 d. The immune organ index was determined every 12 d and the histotomy of chicken small intes- tine in group control and 1% were taken for histological observation on day 24, 36 and 48. [ Result] Treatment group immune organ index was significantly higher than that of the control group and 1% group of small intestinal villus inherent intraformational immune cells number significantly increased (P〈0.01) compared with controls. Day 36 age group and day 48 group immune cells were higher than day 24 group of cell number (P〈 0.01 ). [ Conclusionl Chinese medicinal herb had obvious role in promoting chicken immune organ growth and obvious influence on the quantity change of the intestinal mucosal immune cells.展开更多
BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC ...BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.展开更多
Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits we...Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.展开更多
Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats...Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats. Triiodothyronine ( T3 ) was administered intraperitoneally to correct the low T3 syndrome of septic rats. Blood was collected to examine serum NO and thyroid hormone concentration. Intestinal mucosa iNOS activity was assayed using immunochemical stain. Results Mortality rate in the prevention group was significantly lower than the septic group (Log rank = 3. 85, P 【 0.05). Serum NO concentration was significantly lower in the prevention group (F=19.6,F【0.01). The degree of inflammatory injury of intestinal mucosa was much milder in the prevention group than in the septic group (x2 = 5.303,P【0. 05). Mucosa iNOS activity was also significantly lower in the prevention group (x2 = 4. 876, P【0. 01). Conclusion Thyroid hormone protects the intestinal mucosa barrier inhibiting the expression of展开更多
Hemorrhagic shock is a common clinical emergency case. Successful treatment is usually accomplished by surgical control of hemorrhage and restoration of tissue perfusion. The fluid resuscitation method in the presurgi...Hemorrhagic shock is a common clinical emergency case. Successful treatment is usually accomplished by surgical control of hemorrhage and restoration of tissue perfusion. The fluid resuscitation method in the presurgical care of the hypotensive trauma patients is controversial. Current guidelines for presurgical treatment of patients with hemorrhagic shock recommend rapid volume resuscitation to normal blood pressure as quickly as possible.展开更多
Background Massive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study w...Background Massive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study was conducted to investigate the early effects of hypertonic and isotonic saline solutions on heme oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats with hemorrhagic shock. Methods A model of severe hemorrhagic shock was established in 21 Sprague-Dawley rats. The rats were randomly divided into sham, normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS) groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and resuscitation using the SYBR Green I fluorescence quantitative reverse transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin V/propidium iodide double staining, and flow cytometry. Results In the early stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in the NS group was higher than that in the HTS group (P 〈0.01). Among the three groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression; however, the differences were not significant. There was a significant negative correlation between HO-1 mRNA expression and apoptosis in the small intestinal mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation. Conclusions In this rat model of severe hemorrhagic shock, HTS resuscitation with a small volume is more effective than NS resuscitation in reducing apoptosis of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal mucosa may be one of the molecular mechanisms of HTS in the resuscitation of hemorrhagic shock.展开更多
[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural ...[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.展开更多
Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is ve...Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is very complex and involves several major and minor contributors,employing different inflammatory pathways which have different roles in different patients.Although new and powerful medical treatments are available,many are biological drugs or immunosuppressants,which are associated with significant side effects and elevated costs.As a result,the need for predicting disease course and response to therapy is essential.Major attempts have been made at identifying clinical characteristics,concurrent medical therapy,and serological and genetic markers as predictors of response to biological agents.Only few reports exist on how mucosal/tissue markers are able to predict clinical behavior of the disease or its response to therapy.The aim of this paper therefore is to review the little information available regarding tissue markers as predictors of response to therapy,and reevaluate the role of tissue factors associated with disease severity,which can eventually be ranked as "tissue factor predictors".Five main categories are assessed,including mucosal cytokines and chemokines,adhesion molecules and markers of activation,immune and non-immune cells,and other mucosal components.Improvement in the design and specificity of clinical studies are mandatory to be able to classify tissue markers as predictors of disease course and response to specific therapy,obtain the goal of achieving "personalized pathogenesisoriented therapy" in IBD.展开更多
To study the biopathological characteristics of the transitional mucosa adjacent to rectal carcinoma, 34 cases were subjected to mucin histochemical and immunohistochemical study to observe the expression of p53 and ...To study the biopathological characteristics of the transitional mucosa adjacent to rectal carcinoma, 34 cases were subjected to mucin histochemical and immunohistochemical study to observe the expression of p53 and p21 protein in distal mucosa adjacent to rectal carcinoma and its relationship to the mucin change. The expression of p53 protein was found in 29. 4 % (10/34) of distal transitional mucosa in the cytoplasm of goblet cells, and its positive staining was within 4 cm from carcinoma margin. A11 p53 positive mucosa was transitional mucosa. Overexpression of p21 protein was found in 26.5 % (9/34) of distal transitional mucosa in cytoplasm of crypt cells, and its positive staining was within 2 cm from carcinoma margin. There was no relationship between the expression of p53 and p21 protein in carcinoma and that in transitional mucosa ( P >0.05). These findings indicated that there was aberrant alteration of p53 and p21 genes in transitional mucosa adjacent to colorectal carcinoma, which provided further evidence that transitional mucosa was an unstable pre cancerous change. The aberrant mucin change and genetic alteration in distal mucosa of rectal cancer is within 4 cm.展开更多
An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that co...An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,however,is largely observational,requiring repeated invasive endoscopic examinations,sometimes with mucosal biopsies.Other indirect imaging methods may play a role in this assessment along with other surrogate markers,including intestinal permeability.These measurements may have significant limitations that prohibit precise correlation with symptom-based disease activity indices in clinical trials.This likely reflects the dynamic nature of this evolving and individualized inflammatory process that tends to be focused,but not limited,to the mucosa of the intestinal tract.展开更多
Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this stud...Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...展开更多
OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decrease...OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.展开更多
The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their r...The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein(CRP) levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls(P〈0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase(P〈0.05), and correlated with CRP levels(r=0.578, P〈0.01). IL-17 R expression levels were higher in active UC patients than in healthy con-trols(P〈0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.展开更多
The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the cl...The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional sopport. The signs of nutritional condition and hepatic function were massured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC PED) to acquire the defferent effects among the different nutritional support performence. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant ( P <0 05). There was no obvious change in L/M ratio in the postoperative patients in the EN group ( P >0.05), but there was significant difference in L/M between TPN group and CON group ( P <0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support mathod in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection.展开更多
Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approach...Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.展开更多
文摘The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanoparticles AT-R@CMSN exhibiting geometrical chiral structure were designed to improve the surface/interface roughness in nanoscale,and employed as the hosting system for insoluble drugs nimesulide(NMS)and ibuprofen(IBU).Once performing the delivery tasks,AT-R@CMSN with rigid skeleton protected the loaded drug and reduced the irritation of drug on gastrointestinal tract(GIT),while their porous structure deprived drug crystal and improved drug release.More importantly,AT-R@CMSN functioned as“antiskid tire”to produce higher friction on intestinal mucosa and substantively influencedmultiple biological processes,including“contact”,“adhesion”,“retention”,“permeation”and“uptake”,compared to the achiral S@MSN,thereby improving the oral adsorption effectiveness of such drug delivery systems.By engineering AT-R@CMSN to overcome the stability,solubility and permeability bottlenecks of drugs,orally administered NMS or IBU loaded AT-R@CMSN could achieve higher relative bioavailability(705.95%and 444.42%,respectively)and stronger anti-inflammation effect.In addition,AT-R@CMSN displayed favorable biocompatibility and biodegradability.Undoubtedly,the present finding helped to understand the oral adsorption process of nanocarriers,and provided novel insights into the rational design of nanocarriers.
基金supported by grants from Zhejiang Province Traditional Chinese Medicine Scientific Research Fund(2011-ky1-001-164 and 2016ZB066)Public Welfare Projects of Ministry of Science of Zhejiang Province(20130101120016)
文摘BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1 beta, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1 beta converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1 beta, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1 beta and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1 beta and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines, including IL-1 beta and IL-18. Our animal data may be applicable in clinical practice.
基金National Natural Science Foundation of China(31872387)Zhejiang Provincial Natural Science Foundation(Sodium butyrate promotes restoration of intestinal barrier induced by oxidative stress in piglets through AMPK mediated mitophagy)and Zhejiang Provincal Key R&D Project(2019C02051).
文摘Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin.Each treatment has six replicates of six pigs.After 14 days,6 pigs from each treatment were selected and the jejunal samples were collected.Results:Results showed that supplemental tributyrin increased(P<0.05)villus height and villus height:crypt depth of weaned pigs.Pigs fed tributyrin had greater(P<0.05)RNA/DNA and protein/DNA ratios than pigs on the control group.The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated(P<0.05)in pigs fed the tributyrin diet.Dietary tributyrin supplementation lowered(P<0.05)the malondialdehyde and hydrogen peroxide(H2O2)content in jejunum,enhanced(P<0.05)the mitochondrial function,as demonstrated by decreased(P<0.05)reactive oxygen species level and increased(P<0.05)mitochondrial membrane potential.Furthermore,tributyrin increased(P<0.05)mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions,including peroxisomal proliferator-activated receptor-γcoactivator-1α,mitochondrial transcription factor A,nuclear respiratory factor-1 in the jejunum.Supplementation with tributyrin elevated(P<0.05)the phosphorylation level of AMPK and inhibited(P<0.05)the phosphorylation level of mTOR in jejunum compared with the control group.Conclusions:These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth,extenuates oxidative stress,improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.
基金Funded the Project of Science and Technology in Hebei Province(08820412D,12820408D,12820421DShi-jiazhuang City Science and Technology Bureau Project(07150193A)Hebei Normal University of Science&Technolo-gy Doctor Fund(2007YB002)
文摘[Objective] The aim was to explore the mechanism of Chinese medicinal herb to enhance the body's immune. [Method] The quantitative distribution of immunocytes in chicken small intestinal mucosa lymphoid tissue-secretory type immune globulin cell A were dynamic observed to research chicken immune organ growth with histology conventional slice technology and immunohistochemistry dye. 1 day age healthy roosters were divided into 3 groups: the group 3 was control group. 1% and 0.5% concentration of Chinese herbal medicine immunopotentiator drinking water were added in the group 1 and 2 in continuous 60 d. The immune organ index was determined every 12 d and the histotomy of chicken small intes- tine in group control and 1% were taken for histological observation on day 24, 36 and 48. [ Result] Treatment group immune organ index was significantly higher than that of the control group and 1% group of small intestinal villus inherent intraformational immune cells number significantly increased (P〈0.01) compared with controls. Day 36 age group and day 48 group immune cells were higher than day 24 group of cell number (P〈 0.01 ). [ Conclusionl Chinese medicinal herb had obvious role in promoting chicken immune organ growth and obvious influence on the quantity change of the intestinal mucosal immune cells.
基金Suzhou Science and Technology Program,No.SLT202005Suzhou Municipal Commission of Health and Family Planning,No.LCZX202031+1 种基金Suzhou New District Science and Technology Plan,No.2019Z009Independent Innovation Project of National High Tech Development Zone Hospital,No.SGY2018C03.
文摘BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.
基金Natural Science Research Project of Henan Province Education Department(NO.2006310021)
文摘Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.
文摘Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats. Triiodothyronine ( T3 ) was administered intraperitoneally to correct the low T3 syndrome of septic rats. Blood was collected to examine serum NO and thyroid hormone concentration. Intestinal mucosa iNOS activity was assayed using immunochemical stain. Results Mortality rate in the prevention group was significantly lower than the septic group (Log rank = 3. 85, P 【 0.05). Serum NO concentration was significantly lower in the prevention group (F=19.6,F【0.01). The degree of inflammatory injury of intestinal mucosa was much milder in the prevention group than in the septic group (x2 = 5.303,P【0. 05). Mucosa iNOS activity was also significantly lower in the prevention group (x2 = 4. 876, P【0. 01). Conclusion Thyroid hormone protects the intestinal mucosa barrier inhibiting the expression of
文摘Hemorrhagic shock is a common clinical emergency case. Successful treatment is usually accomplished by surgical control of hemorrhage and restoration of tissue perfusion. The fluid resuscitation method in the presurgical care of the hypotensive trauma patients is controversial. Current guidelines for presurgical treatment of patients with hemorrhagic shock recommend rapid volume resuscitation to normal blood pressure as quickly as possible.
文摘Background Massive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study was conducted to investigate the early effects of hypertonic and isotonic saline solutions on heme oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats with hemorrhagic shock. Methods A model of severe hemorrhagic shock was established in 21 Sprague-Dawley rats. The rats were randomly divided into sham, normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS) groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and resuscitation using the SYBR Green I fluorescence quantitative reverse transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin V/propidium iodide double staining, and flow cytometry. Results In the early stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in the NS group was higher than that in the HTS group (P 〈0.01). Among the three groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression; however, the differences were not significant. There was a significant negative correlation between HO-1 mRNA expression and apoptosis in the small intestinal mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation. Conclusions In this rat model of severe hemorrhagic shock, HTS resuscitation with a small volume is more effective than NS resuscitation in reducing apoptosis of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal mucosa may be one of the molecular mechanisms of HTS in the resuscitation of hemorrhagic shock.
基金National Natural Science Foundation of China(31602099)Key Laboratory of Prevention and Control Agents for Animal Bacteriosis(Ministry of Agriculture)(KLPCAAB-2018-06)the Engineering Research Center of Ecology and Agricultural Use of Wetland,Ministry of Education(KF201913)。
文摘[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.
文摘Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is very complex and involves several major and minor contributors,employing different inflammatory pathways which have different roles in different patients.Although new and powerful medical treatments are available,many are biological drugs or immunosuppressants,which are associated with significant side effects and elevated costs.As a result,the need for predicting disease course and response to therapy is essential.Major attempts have been made at identifying clinical characteristics,concurrent medical therapy,and serological and genetic markers as predictors of response to biological agents.Only few reports exist on how mucosal/tissue markers are able to predict clinical behavior of the disease or its response to therapy.The aim of this paper therefore is to review the little information available regarding tissue markers as predictors of response to therapy,and reevaluate the role of tissue factors associated with disease severity,which can eventually be ranked as "tissue factor predictors".Five main categories are assessed,including mucosal cytokines and chemokines,adhesion molecules and markers of activation,immune and non-immune cells,and other mucosal components.Improvement in the design and specificity of clinical studies are mandatory to be able to classify tissue markers as predictors of disease course and response to specific therapy,obtain the goal of achieving "personalized pathogenesisoriented therapy" in IBD.
文摘To study the biopathological characteristics of the transitional mucosa adjacent to rectal carcinoma, 34 cases were subjected to mucin histochemical and immunohistochemical study to observe the expression of p53 and p21 protein in distal mucosa adjacent to rectal carcinoma and its relationship to the mucin change. The expression of p53 protein was found in 29. 4 % (10/34) of distal transitional mucosa in the cytoplasm of goblet cells, and its positive staining was within 4 cm from carcinoma margin. A11 p53 positive mucosa was transitional mucosa. Overexpression of p21 protein was found in 26.5 % (9/34) of distal transitional mucosa in cytoplasm of crypt cells, and its positive staining was within 2 cm from carcinoma margin. There was no relationship between the expression of p53 and p21 protein in carcinoma and that in transitional mucosa ( P >0.05). These findings indicated that there was aberrant alteration of p53 and p21 genes in transitional mucosa adjacent to colorectal carcinoma, which provided further evidence that transitional mucosa was an unstable pre cancerous change. The aberrant mucin change and genetic alteration in distal mucosa of rectal cancer is within 4 cm.
文摘An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,however,is largely observational,requiring repeated invasive endoscopic examinations,sometimes with mucosal biopsies.Other indirect imaging methods may play a role in this assessment along with other surrogate markers,including intestinal permeability.These measurements may have significant limitations that prohibit precise correlation with symptom-based disease activity indices in clinical trials.This likely reflects the dynamic nature of this evolving and individualized inflammatory process that tends to be focused,but not limited,to the mucosa of the intestinal tract.
基金This work was supported in part by grants from the National Key Program for Fundamental Research and Development(Grant No.G1999054203)the National Natural Science Outstanding Youth Foundation of China(Grant No.30125020).
文摘Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...
文摘OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.
基金This study was supported by the National Natural Science Foundation(No.30973871 and No.31071497)and National basic research program of China(No.2010CB530605).
基金supported by the National Natural Science Foundation of China(No.81200283)
文摘The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein(CRP) levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls(P〈0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase(P〈0.05), and correlated with CRP levels(r=0.578, P〈0.01). IL-17 R expression levels were higher in active UC patients than in healthy con-trols(P〈0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.
文摘The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional sopport. The signs of nutritional condition and hepatic function were massured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC PED) to acquire the defferent effects among the different nutritional support performence. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant ( P <0 05). There was no obvious change in L/M ratio in the postoperative patients in the EN group ( P >0.05), but there was significant difference in L/M between TPN group and CON group ( P <0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support mathod in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection.
基金supported by the National Natural Science Foundation of China(NO.81570675,NO.31872742)Clinical Innovation Foundation of Southwest Hospital(SWH2017JCZD-06)Top Talent Training Programme Foundation of Southwest Hospital(SWH2018BJKJ-04).
文摘Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.