Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.

Dietary supplementation of bilberry anthocyanin on growth performance,intestinal mucosal barrier and cecal microbes of chickens challenged with Salmonella Typhimurium

Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.

Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats

AIM: To observe the protective effect of glucagon-like peptide-2(GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase(ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14 th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A(Ig A) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group.RESULTS: In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced Ig A expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group(P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group(P < 0.01).CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal Ig A and reduced bilirubin and endotoxin.

Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy

BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

Protective effect of exogenous IGF-I on the intestinal mucosal barrier in rats with severe acute pancreatitis

BACKGROUND:Severe acute pancreatitis(SAP) can result in intestinal mucosal barrier(IMB)dysfunction.This study was undertaken to demonstrate the effect of IGF-I on the intestinal mucosal barrier in rats with SAP and its possible mechanisms.METHODS:Seventy-two male Wistar rats were randomly divided into three groups:a sham operation(SO group,n=24),a SAP group not treated with IGF-I(SAP group,n=24),and a SAP group treated with IGF-I(IGF-I group,n=24).SAP was induced in the rats by injecting 5.0%sodium taurocholate into the biliary-pancreatic duct.The SO rats were given an infusion of normal saline instead.The rats in the IGF-I group underwent the SAP procedure and were given a subcutaneous injection of IGF-I at 30 minutes before the operation and at 3 hours after the operation.Eight rats in each group were sacrificed at 6,12 and 24 hours after operation.Apoptosis of mucosal cells in the small intestine was determined by TUNEL.The levels of endotoxin and DAO and serum amylase were also measured.Pathologic changes in the small intestine were monitored.Changes of bax and bcl-2 mRNA expression in the small intestine were determined by reverse transcription polymerase chain reaction(RT-PCR).RESULTS:The levels of serum amylase were lower in the IGF-I group than in the SAP group at all three time points(P<0.05).The levels of endotoxin in the IGF-I group were higher than those in the SAP group at 6 hours,but lower in the IGF-I group than in the SAP group at 12 and 24 hours(P<0.05).The levels of diamine oxidase were higher in the IGF-I group at 6 hours but lower than those in the SAP group at 12 and 24 hours.The pathological score of the small intestine was lower in the IGF-I group than in the SAP group,and the difference was statistically significant at 12 and 24 hours.The pathologic changes observed under electron microscopy were better in the IGF-I group than those in the SAP group.The apoptosis index of intestinal epithelial cells was significantly decreased in the IGF-I group compared with the SAP group.Compared with the SO group,the mRNA expression levels of bax were increased at each time point in the SAP group,and were significantly decreased in the IGF-I group as compared with the SAP group at each time point(P<.05).The expression levels of bcl-2 were weak and not different between the SO group and the SAP group(P>0.05).They were significantly increased in the IGF-I group versus the SO and SAP groups(P<0.05).The ratio of bax and bcl-2 mRNA expression levels at each time point in the SAP group were significantly higher than those in the SO group,but they were obviously decreased in the IGF-I group.CONCLUSIONS:Exogenous IGF-I seems to protect mucosal cells in the small intestine against SAP-induced apoptosis and could alleviate SAP-induced injury of the intestinal mucosa.The underlying mechanisms include enhanced mRNA expression of bcl-2 and inhibition of bax mRNA expression.

Diverse expression patterns of mucin 2 in colorectal cancer indicates its mechanism related to the intestinal mucosal barrier

BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

Effects of Faecalibacterium prausnitzii intervention on immune response, intestinal flora and intestinal mucosal barrier of mice with ulcerative colitis

Objective: To study the effects of Faecalibacterium prausnitzii intervention on immune response, intestinal flora and intestinal mucosal barrier of mice with ulcerative colitis (UC). Methods: C57BL/6J mice were randomly divided into control group, UC group and Faecalibacterium prausnitzii group, the latter two groups were made into UC models by trinitrobenzene sulfonic acid enema and F. prausnitzii group were given intragastric administration of F. prausnitzii solution for intervention. The differences in immune response, intestinal flora, and intestinal mucosal barrier were compared among the three groups after 7 days of intervention. Results: The interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) contents in serum, the fork head box P3 (Foxp3), zonula occludens-1 (ZO-1), occludin, claudin-1 and claudin-2 expression in intestinal mucosa as well as the number of bifidobacterium and lactobacillus in feces of the UC group were significantly lower than those of the control group whereas the interleukin-17 (IL-17), diamine oxidase (DAO) and D-lactic acid (D-LA) contents in serum, the retinoid-related orphan nuclear receptor γt (RORγt) expression in intestinal mucosa as well as the number of enterobacter and enterococcus in feces were significantly higher than those of the control group (P<0.05);IL-10 and TGF-β1 contents in serum, Foxp3, ZO-1, occludin, claudin-1 and claudin-2 expression in intestinal mucosa as well as the number of bifidobacterium and lactobacillus in feces of the F. prausnitzii group were significantly higher than those of the UC group whereas IL-17, DAO and D-LA contents in serum, RORγt expression in intestinal mucosa as well as the number of enterobacter and enterococcus in feces were significantly lower than those of the UC group (P<0.05). Conclusion: Faecalibacterium prausnitzii intervention can improve the Th17/Treg immune response, intestinal flora and intestinal mucosal barrier in UC mice.

Effect of Xingnaojing injection on intestinal mucosal barrier in septicemia and intracerebral hemorrhage mice

OBJECTIVE Xingnaojing injection(XNJ) is an extracts of Angong Niuhuang Pill that is a well-known traditional Chinese medicine used for the treatment of septicemia and stroke.This study aims to investigate the effect of XNJ on intestinal mucosal barrier in septicemia and intracerebral hem.orrhage(ICH) mice models.METHODS The septicemia mice models were induced by intravenous in.jection with lipopolysaccharide(20 mg·kg^(-1)).And the ICH mice models were made by intrastriatal injec.tion of bacterial collagenase.The septicemia animals were treated intravenously with XNJ at dose of2.5,5,10,or 15 mL·kg^(-1).The ICH animals were treated intravenously with XNJ at dose of 10 mL·kg^(-1).Thereafter,the permeability of intestinal mucosa was assayed by FITC-D method.RESULTS Com.pared with the control group(44.72±4.30),the permeability of intestinal mucosa in the mice in septice.mia group(233.68±28.18) was significantly increased(P<0.01).Treatment with XNJ at dose of 5,10,and 15 mL·kg^(-1) reduced the permeability of intestinal mucosa(150.45±17.52,139.21±17.05,132.55±18.88,respectively,P<0.01) except 2.5 mL·kg^(-1)(240.71±21.42,P>0.01);Compared with sham group(57.88±7.31),the permeability of intestinal mucosa in the mice of ICH(282.25±23.78) was significantly in.creased(P<0.01).Treatment with XNJ(10 mL·kg^(-1)) in the mice of ICH group ameliorated the change of permeability in intestinal mucosa(148.83±15.86,P<0.01).CONCLUSION XNJ exhibits the protec.tive effect on the intestinal mucosal barrier in septicemia and ICH,which will prevent the endotoxin to penetrate the intestinal mucosa and then to enter the circulation in infections and stress.

Protective effect of perioperative recombinant human growth hormone application on intestinal mucosal barrier function in patients with intestinal obstruction and the assessment of immune inflammatory response

Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.

Effect of glutamine nutrition support on the intestinal mucosal barrier function and inflammatory response in patients with severe acute pancreatitis

Objective:To study the effect of glutamine nutrition support on the intestinal mucosal barrier function and inflammatory response in patients with severe acute pancreatitis.Methods:Patients with severe acute pancreatitis who were treated in Pengzhou People's Hospital between May 2014 and November 2016 were selected as the research subjects and randomly divided into two groups, control group received conventional symptomatic treatment and conventional enteral nutrition intervention, and Gln group received conventional symptomatic treatment and glutamine enteral nutrition intervention. The contents of intestinal mucosal barrier damage markers and inflammatory mediators in serum as well as the expression of inflammatory signaling molecules in peripheral blood were detected before and after treatment;the number of intestinal flora was detected after treatment.Results:After treatment, LPS, DAO, HBD2, TNF-α, sTREM-1, IL-1β and IL-6 levels in serum as well as TLR4, NF-kB, MyD88 and p38MAPK mRNA expression in peripheral blood mononuclear cells of both groups of patients were significantly lower than those before treatment, LPS, DAO, HBD2, TNF-α, sTREM-1, IL-1β and IL-6 levels in serum as well as TLR4, NF-kB, MyD88 and p38MAPK mRNA expression in peripheral blood mononuclear cells of Gln group after treatment were significantly lower than those of control group, and the number of lactobacillus, bifidobacterium and bacteroides were significantly higher than those of control group while the number of escherichia coli and enterococcus were significantly lower than those of control group.Conclusion: Glutamine nutrition support for severe acute pancreatitis can reduce the intestinal mucosal barrier function injury and inhibit the inflammatory response activation.

Intestinal mucosal barrier in functional constipation:Dose it change?

BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.

Effect of AngongNiuhuang Pill on neurological function and intestinal mucosal barrier in intracerebral hemorrhage mice

OBJECTIVE To investigate the effect and mechanism of AngongNiuhuang Pill(AGNH)on neurological function and intestinal mucosal barrier in intracerebral hemorrhage(ICH).METHODS Male CD-1 mice were randomly divided into sham,ICH,AGNH 0.1 g · kg^(-1),AGNH 0.2 g · kg^(-1),and AGNH 0.4 g·kg^(-1) groups.The ICH mice models were prepared by intrastriatal injection with collage.nase using a stereotaxic frame.Garcia test was used to evaluate the neurological function of mice.The brain water content was measured with dry/wet weight method.The permeability of intestinal mucosa was detected by FITC-D method.H&E staining was used to observe the pathological changes of intestine.The content of endotoxin in blood and the expressions of ZO-1,occludin in intestinewere also investigated.RESULTS After AGNH administration,the neurological score of mice was increased,and the brain water content was decreased(P<0.01).AGNH attenuated the ICH-induced increase of perme.ability of intestinal mucosa(P<0.01).Treatment with AGNHnot only alleviated the pathological changes of the intestine but alsoreduced the endotoxin content in blood(P<0.01).The expressions of ZO-1,occludinin AGNH groups were significantly increased compared with that of ICH group(P<0.05).CONCLUSION AGNH improves the neurological dysfunction in ICH mice and the mechanism of action is implicated in protecting the intestinal mucosa.

Value of serum procalcitonin content in severe acute pancreatitis for evaluating the infection degree and intestinal mucosal barrier function

Objective: To explore the value of serum procalcitonin content in severe acute pancreatitis for evaluating the infection degree and intestinal mucosal barrier function. Methods: A total of 68 patients with severe acute pancreatitis who were treated in our hospital between January 2015 and September 2017 were selected as pancreatitis group, and 50 healthy volunteers who underwent physical examination in this hospital during the same period were selected as normal control group. The differences in serum levels of PCT, inflammatory factors and intestinal mucosal barrier function indexes were compared between the two groups, and Pearson test was used to evaluate the correlation between PCT content and severe acute pancreatitis. Results: Serum PCT content of pancreatitis group was higher than that of control group;serum IL-6, IL-10 and TNF-α contents were higher than those of control group;serum D-Lactate, DAO and Endotoxin contents were higher than those of control group. Pearson test showed that the serum PCT content of patients with severe acute pancreatitis was directly correlated with the degree of infection and intestinal mucosal barrier dysfunction. Conclusion:Serum PCT content abnormally increases in severe acute pancreatitis, and the specific content is directly correlated with the degree of infection and intestinal mucosal barrier dysfunction.

Effect of somatostatin combined with omeprazole on serum inflammatory factors and intestinal mucosal barrier function in severe acute pancreatitis

Objective:To investigate the effect of somatostatin combined with omeprazole on serum inflammatory factors and intestinal mucosal barrier function in severe acute pancreatitis. Methods: patients with severe acute pancreatitis who were treated in Zigong Third People's Hospital between August 2014 and December 2017 were chosen and divided into two groups by random number table method. Control group received conventional + omeprazole treatment, combined group received conventional + somatostatin + omeprazole treatment and the treatment lasted for 1 week. The differences in serum levels of inflammatory factors, chemokines and intestinal mucosal barrier function indexes were compared between the two groups immediately after admission and after 1 week of treatment.Results: After 1 week of treatment, serum IL-1β, IL-8, IL-18, hs-CRP, MCP-1, FKN, CINC, D-Lactate, DAO, Endotoxin and FABP levels of both groups significantly decreased and serum IL-1β, IL-8, IL-18, hs-CRP, MCP-1, FKN, CINC, D-Lactate, DAO, Endotoxin and FABP levels of combined group were significantly lower than those of control group.Conclusion: Somatostatin combined with omeprazole therapy for severe acute pancreatitis can effectively alleviate the inflammatory response and protect the intestinal mucosal barrier function.

Effects of cefixime on the systemic inflammatory stress response and intestinal mucosal barrier injury in children with infective enteritis

Objective:To investigate the effects of cefixime on the systemic inflammatory stress response and intestinal mucosal barrier injury in children with infective enteritis.Methods:A total of 80 children with infective enteritis who were treated in the hospital between March 2016 and August 2017 were divided into group A (n=40) and group B (n=40) according to the random number table method. Group A received cefaclor anti-infective therapy, group B received cefixime therapy, and both therapies lasted for 1 week. The differences in serum levels of inflammatory mediators, oxidative stress indexes and intestinal mucosal injury markers were compared between the two groups before and after treatment.Results: Before treatment, the differences in serum levels of inflammatory mediators, oxidative stress indexes and intestinal mucosal injury markers were not statistically significant. After 1 week of treatment, serum inflammatory mediators IL-8 and TNF-α levels of group B were lower than those of group A whereas IL-10 level was higher than that of group A;serum oxidative stress indexes ROS and MDA levels were lower than those of group A whereas GSH-Px and CAT levels were higher than those of group A;serum intestinal mucosal injury markers DAO, D-Lactate, FABP and GST levels were lower than those of group A.Conclusion: Cefixime anti-infective therapy can effectively inhibit the inflammatory stress response and reduce the intestinal mucosal barrier injury in children with infective enteritis.

Effect of triple viable capsule combined with antibiotic therapy on the inflammatory factors and intestinal mucosal barrier function in patients with spontaneous bacterial peritonitis

Objective: To study the effect of triple viable capsule combined with antibiotic therapy on the inflammatory factors and intestinal mucosal barrier function in patients with spontaneous bacterial peritonitis. Methods: Patients with cirrhosis combined with spontaneous bacterial peritonitis who were treated in Traditional Chinese Medicine Hospital of Shehong County between March 2015 and October 2017 were selected and randomly divided into the observation group who accepted triple viable capsule combined with antibiotic therapy and the control group who accepted conventional symptomatic treatment. The levels of inflammatory factors and intestinal mucosal barrier markers in serum as well as the number of intestinal flora in feces were detected before treatment and 2 weeks after treatment. Results: Compared with those of same group before treatment, PCT, CRP, sTREM-1, MCP-1, TNF-α, IFN-γ, DAO, D-lactic acid, LPS, Occludin and ZO-1 levels in serum as well as the number of enterobacter and enterococcus in feces of both groups of patients were lower whereas the number of bifidobacterium, lactobacillus and clostridium leptum were higher after treatment, and PCT, CRP, sTREM-1, MCP-1, TNF-α, IFN-γ, DAO, D-lactic acid, LPS, Occludin and ZO-1 levels in serum as well as the number of enterobacter and enterococcus in feces of observation group after treatment were lower than those of control group whereas the number of bifidobacterium, lactobacillus and clostridium leptum were higher than those of control group. Conclusion: Triple viable capsule combined with antibiotic therapy can inhibit the secretion of inflammatory cytokines and improve the intestinal mucosal barrier function in patients with spontaneous bacterial peritonitis.

Effects of adjuvant raw rhubarb enema therapy on systemic inflammatory stress response and intestinal mucosal barrier function in patients with severe pancreatitis

Objective: To investigate the effects of adjuvant raw rhubarb enema therapy on systemic inflammatory stress response and intestinal mucosal barrier function in patients with severe pancreatitis. Methods: A total of 78 patients with severe pancreatitis treated in the Second People's Hospital of Neijiang, Sichuan, China between December 2016 and September 2018 were included in the study. The patients were divided into control group (n=39) and raw rhubarb group (n=39) by simple randomization. The control group of patients received conventional treatment of severe pancreatitis with western medicine, while the raw rhubarb group of patients received raw rhubarb enema on the basis of the treatment of control group, and the efficacy was evaluated after continuous treatment for 1 week. The differences in serum levels of inflammatory mediators (high mobility group protein B1, C-reactive protein, prostaglandin E2 and tumor necrosis factor α), stress hormones (cortisol and epinephrine) as well as intestinal mucosal barrier function indicators (D-lactate, endotoxin and diamine oxidase) were compared between the two groups of patients before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of inflammatory mediators, stress hormones and intestinal mucosal barrier function indicators between the two groups (P>0.05). After treatment, serum high mobility group protein B1, C-reactive protein, prostaglandin E2 and tumor necrosis factor levels of the observation group were significantly lower than those of the control group;cortisol and epinephrine levels were significantly lower than those of the control group;D-lactate, endotoxin and diamine oxidase levels were significantly lower than those of the control group (P<0.05). Conclusions:Adjuvant raw rhubarb enema therapy on the basis of western medicine can help alleviate the inflammatory stress response and optimize the intestinal mucosal barrier function in patients with severe pancreatitis.

Correlation of NOX1 and NOX2 expression in ulcerative colitis tissue with intestinal mucosal oxidative stress response and barrier function injury

Objective: To study the correlation of NOX1 and NOX2 expression in ulcerative colitis tissue with intestinal mucosal oxidative stress response and barrier function injury. Methods: A total of 69 patients who were diagnosed with ulcerative colitis in Yan'an People's Hospital between May 2015 and March 2017 were selected as the UC group of the research, and 78 patients who were diagnosed with colon polyps were selected as the polyps group of the research. The ulcerative colitis lesion and polyp lesion were collected to detect the expression of NOX1 and NOX2, the generation of oxygen free radicals as well as the contents of apoptosis molecules and mucosal barrier molecules. Results: The mRNA expression and protein expression of NOX1 and NOX2 in the intestinal mucosa of UC group were significantly higher than those of polyps group;LPO, MDA, AOPP, NO, PDCD5 and Bax levels in intestinal mucosa of UC group were significantly higher than those of polyps group and positively correlated with the mRNA expression and protein expression of NOX1 and NOX2 while Bcl-2, Cdx1, Cdx2, galectin-1, galectin-3, OCLN, cingulin and ZO-1 levels were significantly lower than those of polyps group and negatively correlated with the mRNA expression and protein expression of NOX1 and NOX2. Conclusion: The high expression of NOX1 and NOX2 in ulcerative colitis tissue can activate the intestinal mucosal oxidative stress response and result in the intestinal mucosal barrier function injury.