Preservation of superior rectal artery in laparoscopic colectomy:The best choice for slow transit constipation?

Laparoscopic colectomy with ileorectal anastomosis may be beneficial for patients with slow transit constipation who do not respond to conservative treatment,particularly if the superior rectal artery(SRA)is preserved.Several important concerns have been addressed in this commentary.It is important to first go over the definition of surgical procedure as it is used in this text.Second,the current study lacked a control group that had SRA preservation.Thirdly,it would be best to use a prospective,randomized controlled study.Lastly,a description of the mesenteric defect’s state following a laparoscopic colectomy is necessary.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

Effects of a Combination of Fu Zi and Rou Gui on Intestinal Neurotransmitters and Microflora in Rats with Slow Transit Constipation

[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.

A review on slow transit constipation

Slow transit constipation(STC),one of the most common chronic constipation in the clinic,is characterized by prolonged colonic transit time.Pathogenesis is unclear,and abnormalities can be found in enteric nervous system,intestinal neurotransmitters,intestinal smooth muscle,and Cajal stromal cell.Various methods have been used to improve the quality of life of patients with STC,including dietary fiber supplements,various cathartics,prokinetic drugs,and surgical intervention.However,there are still a large number of patients showing poor response to conservative treatment and intolerance to surgical treatment.Patients with STC suffer from severe constipation for long periods of time,faced with heavy economic burden and mental torture.Exploration the pathogenesis of STC to provide a clearer direction for future drug development is needed.

The efficacy and mechanism of fecal microflora transplantation in the treatment of slow transit constipation based on metabonomics anion mode

Background:Fecal microbiota transplantation(FMT)based on the positive ion mode of metabonomics has a good therapeutic benefit for slow transit constipation(STC)patients.However,a piece of comprehensive metabolomics information is yet to be established.The aim of the study was to explore the efficacy and mechanism of FMT in the treatment of STC under metabonomics.Methods:Eight STC patients meeting the set inclusion and exclusion criteria were enrolled and treated with FMT(three times).The Patient Assessment of Constipation-Symptoms(PAC-SYM),weekly total defecation times,and defecation frequency scores of these STC patients were compared before and after treatment.Feces and serum of STC patients before and after treatment were analyzed using 16SrDNA and metabolomics.Results:After FMT treatment,the PAC-SYM score of constipated patients decreased[(5.00±2.94)vs(5.20±2.87)],while the number of complete defecations per week increased[(2.00±1.79)vs(1.69±1.80)].The score of defecation frequency decreased[(0.83±1.03)vs(0.86±0.95)].The metabolites in the feces and serum of patients receiving FMT changed significantly(P<0.05).The results from 16SrDNA analysis showed that theαandβdiversity of the fecal microbiome changed significantly(P<0.05)after transplantation,and the contents of genera Lactobacillus,Bacillus,Succiniclasticum,Cellvibrio,and Escherichia increased in FMT treated patients.Conclusion:FMT may treat STC by increasing the beneficial intestinal flora and metabolites in the anion mode of metabolomics.

Slow transit constipation: A functional disorder becomes an enteric neuropathy

Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations in STC might be considered of neuropathic type.In addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.

Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation

BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.

Normal aspects of colorectal motility and abnormalities in slow transit constipation

Human colonic motility is a relatively difficult topic to investigate. However, the refinement of manometric techniques in recent years enabled us to study both the proximal and distal segments of the viscus. The present paper reviews our knowledge about normal aspects of colorectal motility in man and the abnormalities found in slow transit constipation (STC), one of the most frequent and difficult to treat subtypes of constipation. An internetbased search strategy of the Medline and Science Citation Index was performed using the keywords colon, colonic, colorectal, constipation, slow transit, motility, rectal, rectum in various combinations with the Boolean operators AND, OR and NOT. Only articles related to human studies were used, and manual cross-referencing was also performed. Most of colonic motor activity is represented by single nonpropagated contractions, rarely organized in bursts; this activity is maximal during the day, especially after waking and following meals. In addition, a specialized propagated activity with propulsive features is detectable, represented by high-and low-amplitude propagated contractions. In the severe form of constipation represented by the slow transit type, the above motor activity is completely deranged. In fact, both basal segmental activity (especially in response to meals) and propagated activity (especially that of high amplitude) are usually decreased, and this may represent a physiologic marker of this disorder. Human colonic motor activity is quite a complex issue, still only partly understood and investigated, due to anatomic and physiological difficulties. In recent years, however, some more data have been obtained, even in proximal segments. These data have helped in elucidating, although only in part, some pathophysiological mechanisms of chronic constipation, and especially of the STC subtype.

Subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy for the treatment of slow transit constipation in an aged population:A retrospective control study

AIM To compare the efficacy,improved quality of life,and prognosis in patients undergoing either subtotal colonic bypass with antiperistaltic cecoproctostomy(SCBAC) or subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy(SCBCAC) for the treatment of slow transit constipation.METHODS Between October 2010 and October 2014,aged patients with slow transit constipation who were hospitalized and underwent laparoscopic surgery in our institute weredivided into two groups: the bypass group,15 patients underwent SCBAC,and the bypass plus colostomy group,14 patients underwent SCBCAC. The following preoperative and postoperative clinical data were collected: gender,age,body mass index,operative time,first flatus time,length of hospital stay,bowel movements(BMs),Wexner fecal incontinence scale,Wexner constipation scale(WCS),gastrointestinal quality of life index(GIQLI),numerical rating scale for pain intensity(NRS),abdominal bloating score(ABS),and ClavienDindo classification of surgical complications(CD) before surgery and at 3,6,12,and 24 mo after surgery.RESULTS All patients successfully underwent laparoscopic surgery without open surgery conversion or surgeryrelated death. The operative time and blood loss were significantly less in the bypass group than in the bypass plus colostomy group(P = 0.007). No significant differences were observed in first flatus time,length of hospital stay,or complications with CD > 1 between the two groups. No patients had fecal incontinence after surgery. At 3,6,and 12 mo after surgery,the number of BMs was significantly less in the bypass plus colostomy group than in the bypass group. The parameters at 3,6,12,and 24 mo after surgery in both groups significantly improved compared with the preoperative conditions(P < 0.05),except NRS at 3,6 mo after surgery in both groups,ABS at 12,24 mo after surgery and NRS at 12,24 mo after surgery in the bypass group. WCS,GIQLI,NRS,and ABS significantly improved in the bypass plus colostomy group compared with the bypass group at 3,6,12,and 24 mo after surgery(P < 0.05) except WCS,NRS at 3,6 mo after surgery and ABS at 3 mo after surgery. At 1 year after surgery,a barium enema examination showed that the emptying time was significantly better in the bypass plus colostomy group than in the bypass group(P = 0.007).CONCLUSION Laparoscopic SCBCAC is an effective and safe procedure for the treatment of slow transit constipation in an aged population and can significantly improve the prognosis. Its clinical efficacy is more favorable compared with that of SCBAC. Laparoscopic SCBCAC is a better procedure for the treatment of slow transit constipation in an aged population.

Preservation of superior rectal artery in laparoscopically assisted subtotal colectomy with ileorectal anastomosis for slow transit constipation

BACKGROUND Slow transit constipation(STC)has traditionally been considered as a functional disorder.However,evidence is accumulating that suggests that most of the motility alterations in STC might be of a neuropathic etiology.If the patient does not meet the diagnosis of pelvic outlet obstruction and poorly response to conservative treatment,surgical intervention with subtotal colectomy may be effective.The most unwanted complication of the procedure is anastomotic leakage,however,preservation of the superior rectal artery(SRA)may reduce its incidence.AIM To evaluate the preservation of the SRA in laparoscopically assisted subtotal colectomy with ileorectal anastomosis in STC patients.METHODS This was a single-center retrospective observational study.STC was diagnosed after a series of examinations which included a colonic transit test,anal manometry,a balloon expulsion test,and a barium enema.Eligible patients underwent laparoscopically assisted total colectomy with ileorectal anastomosis and were examined between January 2016 and January 2018.The operation time,blood loss,time to first flatus,length of hospital days,and incidence of minor or major complications were recorded.RESULTS A total of 32 patients(mean age,42.6 years)who had received laparoscopic assisted subtotal colectomy with ileorectal artery anastomosis and preservation of the SRA.All patients were diagnosed with STC after a series of examinations.The mean operative time was 151 min and the mean blood loss was 119 mL.The mean day of first time to flatus was 3.0 d,and the mean hospital stay was 10.6 d.There were no any patients conversions to laparotomy.Post-operative minor complications including 1 wound infection and 1 case of ileus.There was no surgical mortality.No anastomosis leakage was noted in any of the patients.CONCLUSION Laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the SRA can significantly improve bowel function with careful patient selection.Sparing the SRA may protect against anastomosis leakage.

STUDY ON GASTROINTESTINAL MOTILITY IN SLOW TRANSIT CONSTIPATION

Objective To investigate motor activity of gastrointestinal tract in patients with slow transit constipation. Methods 42 patients with STC and 20 healthy controls were included in the study. Each subject underwent colonic transit test, gastric emptying, orocecal transit time, electromyography and anorectal manometry. Results According to transit index, 42 STC patients were divided into 3 types: ①0.5<TI≤1.0, slow rectosigmoid transit 15 cases; ②TI=0.5, colorectal stasis 10 cases; ③0<TI≤0.5, slow colonic transit 17 cases. Gastric emptying rate at the fourth hour was decreased in STC patients than in controls . The mean orocaecal transit time was significantly delayed in the patients . Paradoxical anal sphincter contraction with defecation effort was higher prevalent in patients with slow rectosigmoid transit and colorectal stasis than patients with slow colonic transit. Minimum relaxation volume and maximal rectal tolerable volume were significantly increased in STC patients . Conclusion STC displayed colonic abnormality, and/or pelvic floor dysfunction. In addition, it showed motor abnormalities of upper gut, might be part of a pan enteric motor disorders.

CLINICAL OBSERVATION ON THE TREATMENT OF 34 CASES OF SLOW TRANSIT CONSTIPATION WITH ELECTROACUPUNCTURE

Objective： To explore effective modelity for slow transit constipation （STC） and provide evidence for standardization of pattern identification of STC. Methods： Sixty eight cases of STC patients were randomly and evenly assigned into acupuncture group （n=34） and medication （control） group （n=34）. In acupuncture group, Tianshu （天枢 ST 25） and Zhigou （支沟 TE 6） were punctured and stimulated electrically by setting the parameters of 1 Hz, continuous waves, suitable strength and duration of 30 min. Patients of the control group were ordered to take Tongbionling （bowel-movernent promotion） Capsule, 5 cap sules/time, once daily. Results： After 28 days＇ treatment, symptom scores in both groups were decreased significantly and colonic ejection rates within 72 hours increased considerably in comparison with pre-treatment （ P〈 0, 01 ） ; and the therapeutic effects of acupuncture group were remarkably better than those of control group in lowering symptom score and raising colonic ejection rate （P〈0.01）. Conclusion： Acupuncture is a simple and practical method for the treatment of STC and its therapeutic effect is reliable.

Colectomy for idiopathic slow transit constipation

Objective: To evaluate the intervention of colectomy on a group of patients with idiopathic slow transit constipation (STC). Methods: Thirty-four patients with STC, underwent colectomy during recent 10 years in our department , were subjected and followed for a mean length of 34 months, and their colon transits, defecograms, colonoscopic examination, sex hormone detection, and immunohistochemical studies were retrospectively reviewed. Results: The co-Ionic transit time ranged from 96 to 240 h, with a mean time of 136 h. Eighty-five percent of patients (29/34) accompanied with outlet obstructed constipation, and 50% ( 17/34) showed abnormal sex hormone levels. Colectomy obtained satisfactory results in most patients, except one case of recurrence. Moreover, more neurons positive to nitric oxide synthase (NOS) and lesser to vasoactive intestinal polypeptide (VIP) were seen in the colonic myenteric plexus. Conclusion: Colectomy produces a satisfactory functional outcome in the majority of patients undergoing surgery for slow transit constipation, but accompanied pelvic dysfunction must be corrected simultaneously.

EVALUATION ON THE THERAPEUTIC EFFECT OF DEEP PUNCTURE OF TIANSHU (ST 25) FOR SLOW TRANSIT CONSTIPATION

Objective： To evaluate the short-term and middle-long-term therapeutic effects of deep puncture of Tianshu （天枢 ST 25） for slow transit constipation （STC）. Methods： Sixty cases of STC patients were evenly randomized into Methods： group and medication group. In acupuncture group, electroaoupuncture （EA, 20 Hz, continuous waves and tolerable strength） was applied to bilateral Tienshu （ST 25） for 30 min after deep puncture. The treatment was given once daily, 5 sessions every week, two weeks altogether. Patients of control group were ordered to take Lactulose （ 10mL/time, b. i. d）, two weeks altogether. Cleveland Constipation Score （CCS） and colonic transit time （COT） were used to evaluate the therapeutic effect. Results： After treatment, both COS and COT showed that the therapeutic effect of acupuncture group was significantly superior to that of medication group （P〈0.05）. Six-months＇ follow up showed that the therapeutic effect of acupuncture still maintained in 13 of the 22 cases visited, while that of control group only maintained in 1 of the 19 cases. Conclusion： The therapeutic effect of deep puncture of Tianshu （ST 25） for STC is definite and has a middle-long-term effect. The patients have no any unfavorable reactions.

Proteomic analysis of down-regulated proteins in colonic mucosa of chronic slow transit constipation rats

Objective： To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation （STC） rats with a 2-DE-based proteomic method and analyze the function of these down-regulated proteins so as to provide theoretical basis for the pathogenesis of intestinal mucosa of chronic STC rats. Methods： STC model was established by feeding rats with 8 mg/（kg＇d） diphenoxylate for 120 d. An experimental model of chronic STC rat was used for separation of proteomics from colonic mucosa using two-dimensional electrophoresis （2-DE）. Proteins altered in expressional level were identified by Image Master 2DElite, mass spectrometry, and bibliometrics were applied to identify the differential protein expression and their clinical s observed in the pathogenesis lgn of ificance and function were analyzed. Results： Obvious differential protein expression was STC, including mast cell protease （A1）, non-specific dipeptidase （A2） and chondrosome succinate dehydrogenase precursor （A3）. The expressions of A1, A2 and A3 were down-regulated in the gel graph of STC rats Conclusion： The down-regulation of chondrosome succinate dehydrogenase, mast cell protease as well as non-specific dipeptidase in rat colon suggests the functional impairment of the oxidoreduction of mitochondrion is very important in the genesis and development of STC. The immunological reaction of STC rats is weakened, and the function of digesting and absorbing protein may be damaged to some extent.

Consensus statement AIGO/SICCR:Diagnosis and treatment of chronic constipation and obstructed defecation(partⅠ:Diagnosis)

Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The aim of this project was to develop a consensus for the diagnosis and treatment of chronic constipation and obstructed defecation.The commission presents its results in a "Question-Answer" format,including a set of graded recommendations based on a systematic review of the literature and evidence-based medicine.This section represents the consensus for the diagnosis.The history includes information relating to the onset and duration of symptoms and may reveal secondary causes of constipation.The presence of alarm symptoms and risk factors requires investigation.The physical examination should assess the presence of lesions in the anal and perianal region.The evidence does not support the routine use of blood testing and colonoscopy or barium enema for constipation.Various scoring systems are available to quantify the severity of constipation;the Constipation Severity Instrument for constipation and the obstructed defecation syndrome score for obstructed defecation are the most reliable.The Constipation-Related Quality of Life is an excellent tool for evaluating the patient's quality of life.No single test provides a pathophysiological basis for constipation.Colonic transit and anorectal manometry define the pathophysiologic subtypes.Balloon expulsion is a simple screening test for defecatory disorders,but it does not define the mechanisms.Defecography detects structural abnormalities and assesses functional parameters.Magnetic resonance imaging and/or pelvic floor sonography can further complement defecography by providing information on the movement of the pelvic floor and the organs that it supports.All these investigations are indicated to differentiate between slow transit constipation and obstructed defecation because the treatments differ between these conditions.

Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice

Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table,including control,STC model(model),positive control,and low-,medium-and high-doses ZZD treatment groups(5,10,20 g/kg,namely L,M-,and H-ZZD,respectively),9 mice in each group.Following 2-week treatment,intestinal transport rate(ITR)and fecal water content were determined,and blood and colon tissue samples were collected.Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells.To determine intestinal permeability,serum levels of lipopolysaccharide(LPS),low-density lipoprotein(LDL)and mannose were measured using enzyme-linked immunosorbent assay(ELISA).Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1(ZO-1),claudin-1,occludin and recombinant mucin 2(MUC2).The mRNA expression levels of inflammatory cytokines including tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,IL-4,IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction.Colon indexes of oxidative stress were measured by ELISA,and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1(SIRT1/FoxO1)antioxidant signaling pathway were detected by Western blot.Results Compared with the model group,ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups(P<0.01).Additionally,ZZD treatment notably increased the thickness of mucosal and muscular tissue,elevated the number of goblet cells in the colon of STC mice,reduced the secretion levels of LPS,LDL and mannose,and upregulated ZO-1,claudin-1,occludin and MUC2 expressions in the colon in a dose-dependent manner,compared with the model group(P<0.05 or P<0.01).In addition,ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway(P<0.05 or P<0.01).Conclusion ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

电针对慢传输型便秘大鼠肠道运动及促炎性因子表达影响

目的观察电针下合穴“足三里”“上巨虚”对慢传输型便秘(STC)大鼠肠道运动及促炎性因子表达的影响。方法24只健康清洁级SD大鼠随机分为空白组、模型组、药物组和电针组,每组各6只。采用复方地芬诺酯混悬液10 mg·kg^(-1)剂量灌胃制备STC大鼠模型,每天1次,连续14 d。空白组予等剂量0.9%氯化钠溶液灌胃。电针组给予双侧“足三里”“上巨虚”电针治疗,选择疏密波,频率2/50 Hz,电流大小以局部肌肉轻微抖动为度,每次治疗20 min,每天1次,连续治疗14 d。药物组予枸橼酸莫沙必利片混悬液按照1.37 mg·kg^(-1)、1 mL·100 g^(-1)剂量灌胃治疗,疗程同上。观察各组治疗后首粒黑便排出时间、小肠推进率,采用HE染色观察结肠组织病理形态学变化,采用Western-blot法检测肠道肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、CD68蛋白表达。结果模型组大鼠首粒黑便排出时间较空白组显著加长,小肠推进率显著降低(P<0.05);药物组和电针组大鼠经治疗后,与模型组比较,首粒黑便排出时间显著减少、小肠推进率显著提高(P<0.05)。HE染色可见造模后大鼠结肠黏膜组织出血,组织形态学结构破坏,伴上皮细胞变性坏死及炎性细胞浸润;电针和药物治疗能够减少炎性细胞浸润,改善组织形态学变化。Western-blot结果显示,模型组大鼠TNF-α、IL-1β、CD68蛋白表达较空白组显著升高(P<0.05);药物组和电针组大鼠经治疗后,结肠组织TNF-α、IL-1β、CD68蛋白表达较模型组显著降低(P<0.05)。结论电针治疗能够改善STC大鼠肠道运动功能,修复结肠组织病理形态学改变,其机制可能与下调TNF-α、IL-1β、CD68蛋白表达,抑制炎性反应有关。

基于肠道菌群与血清代谢组学联用技术探讨首荟通便胶囊治疗慢性传输型便秘的机制

目的:探讨首荟通便胶囊(SHTB)治疗慢性传输型便秘(STC)的作用机制。方法:将80只SD大鼠随机分为对照组,模型组,莫沙必利(MOS,10 mg/kg)组,SHTB高(630 mg/kg)、低(210 mg/kg)剂量组,每组16只。模型组和各给药组灌胃复方地芬诺酯片10 mg/kg以诱导STC大鼠模型,对照组灌胃等体积纯水,1次/d,连续14 d。第15天开始,对照组、模型组灌胃生理盐水,MOS组、SHTB高和低剂量组灌胃相应剂量药物,1次/d,连续7 d。末次给药后,每组6只大鼠灌胃墨汁,测定首粒黑便时间、24 h排便粒数及墨汁推进率;HE染色观察结肠组织病理学改变;每组10只大鼠,16S rDNA法检测肠道菌群,超高效液相色谱串联质谱技术行血清代谢组学分析。结果:与模型组比较,SHTB高剂量组首粒黑便时间缩短,24 h排便粒数与墨汁推进率增加(P<0.05),病理表现改善;肠道菌群厚壁菌门/拟杆菌门比值、疣微菌门丰度减小,Prevotella_9、Prevotellaceae_UCG-001丰度增大(P<0.05)。血清代谢组学分析共筛选出8种差异代谢产物,涉及组氨酸代谢、β-丙氨酸代谢、初级胆汁酸生物合成、胆汁分泌、嘌呤代谢、初级胆汁酸合成传导和其代谢传导等7条代谢通路。结论:SHTB治疗STC的作用机制可能与调节肠道菌群结构,进而调节胆汁酸代谢等相关通路有关。

养阴润肠方联合针刺治疗老年慢传输型便秘临床观察

目的:观察养阴润肠方联合针刺治疗老年慢传输型便秘临床疗效。方法:选取老年慢传输型便秘患者84例,根据随机数字表法分为两组各42例。对照组予针刺治疗,治疗组在对照组基础上联合养阴润肠方治疗,疗程均为4周。观察两组患者临床疗效、中医证候评分、血清胃肠激素水平、结肠动力变化、肠道菌群数量检测及便秘患者生活质量量表(PAC-QOL)评分。结果:治疗组总有效率92.86%高于对照组的76.19%(P﹤0.05)。治疗后两组中医证候评分、血清VIP、5-HT水平、右半结肠通过时间、左半结肠通过时间、全结肠通过时间、大肠埃希菌平均数量、PAC-QOL评分均较治疗前明显降低(P﹤0.05),且治疗组各指标水平均低于对照组(P﹤0.05);治疗后两组乳酸杆菌数量、双歧杆菌数量、血清SP水平较治疗前上升(P﹤0.05),且治疗组均高于对照组(P﹤0.05)。结论:养阴润肠方联合针刺治疗老年慢传输型便秘可提高肠道动力,改善肠道菌群和胃肠激素水平,有效缓解临床症状,提高患者生活质量。