Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis

AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome (D-IBS).

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.

Effect of Modified Sinisan (四逆散) on Anorectal Manometry of the Constipation Predominant Type of Irritable Bowel Syndrome

Objective: To explore the mechanism in patients with irritable bowel syndrome (IBS) of the constipation predominant type and observe the therapeutic effects of Sinisan (四逆散, SNS). Methods: Forty -seven IBS patients with the constipation predominant type were randomly divided into the treated group ( n =24) and the control group ( n =23). Another group of 22 healthy subjects was set up for healthy control. The treated group was treated with modified SNS, and the control group was treated with Cisapride, the therapeutic course for both groups was 8 weeks. The changes of symptom scoring and anorectal manometry (the anorectal resting pressure, anal tract systolic pressure, anal tract diastolic pressure, rectal threshold feeling, maximal tolerance volume of rectum, and rectum compliance) of these two groups were recorded respectively and compared with each other. Results: Compared with the healthy control group, the rectal threshold feeling, maximal tolerance volume of rectum and rectal compliance of the treated groups got reduced significantly before treatment ( P <0.05). After treatment, the symptom scoring, rectal threshold feeling and maximal tolerance volume of rectum were improved in both groups ( P <0.05), and the improvement of the treated group was more significant than that of the control group( P <0.01). The total effective rate and recurrence rate of the treated group were superior to those of the control group significantly ( P <0.05, P <0.01).Conclusion: SNS has good effect on IBS of the constipation predominant type.

Efficacy and Safety of Traditional Chinese Patent Medicine Qizhi Weitong Granules(气滞胃痛颗粒)in Irritable Bowel Syndrome with Predominant Constipation:A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Objective:To systematically review the efficacy and clinical safety of Qizhi Weitong Granules(气滞胃痛颗粒)(QZWT)in the treatment of irritable bowel syndrome with predominant constipation(IBS-C).Methods:Randomized controlled trials(RCTs)of QZWT in patients with IBS-C were retrieved from Pub Med,EMBASE,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang,Chinese Scientific Journals Database(VIP),and Chinese Biological Medical Database(CBM)from inception to December 3,2022.Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis(TSA)were performed by Review Manager 5.4,Stata and TSA software.Results:A total of 4 RCTs and 368 patients with IBS-C were included in this study.The findings of the meta-analysis indicated that the cure and efficacy rate of the experimental group was significantly higher than that of the control group[RR=2.19;(95%CI,1.35–3.55),P<0.01;RR=1.14;(95%CI,1.03–1.27),P<0.05],while the result of Bristol Score was negative.The funnel plot was probably symmetry,and the P value was>0.05 in the Egger test,which confirmed the nonexistence of significant publication bias in this outcome.TSA showed the cumulative z-value crossed the traditional threshold and TSA threshold,while it didn't get to the required information size.Finally,2 studies reported adverse events after QZWT treatment,including 3 cases of diarrhea.No serious adverse events were reported.Conclusion:QZWT was an effective and safe complementary therapy in the treatment of IBS-C with no obvious adverse reactions.TSA analysis confirmed our meta-analysis results.Therefore,QZWT may be a potential candidate for the treatment of IBS-C.However,due to the limited quality of current studies,more long-term,randomized,double-blinded clinical trials are needed in future studies.

High risk of temporomandibular disorder in irritable bowel syndrome: Is there a correlation with greater illness severity?

AIMTo investigate the prevalence and the risk of temporomandibular disorders (TMDs) in patients with irritable bowel syndrome (IBS) (including each subtype: constipation, diarrhoea, and mixed) compared to the general population.METHODSBetween January 2014 and December 2015 we enrolled consecutively adult patients diagnosed with IBS at the outpatient clinic of the University of Salerno and healthy controls (HC) without IBS. At enrollment, we analyzed all patients for the presence of TMDs according to the Research Diagnostic Criteria for TMD.RESULTSWe enrolled 91 IBS patients (23 IBS-D, 30 IBS-C and 38 IBS-M) and 57 HC in the study. We found a higher risk of having TMD (OR = 3.41, 95%CI: 1.66-7.01) compared to the HC. The risk of having TMD was independent of IBS-subtype. Multiple regression analysis showed that facial pain was positively related to abdominal pain and higher level of depression.CONCLUSIONIBS patients had a more than three times greater risk of TMD compared to HC. The risk of having TMD was similar in different IBS subtypes. IBS patients that also fulfilled criteria for TMD seem to share along with chronic facial and abdominal pain a significant co-occurrence with psychiatric disorders and female preponderance.

How can probiotic improve irritable bowel syndrome symptoms?

The onset and manifestations of irritable bowel syndrome(IBS)is associated with several factors,and the pathophysiology involves various central and peripheral mechanisms.Most studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with IBS.Numerous clinical trials have assessed the efficacy of probiotics for IBS with controversial conclusions.Several clinical trials have suggested that probiotics can improve global IBS symptoms,while others only improve individual IBS symptoms,such as bloating scores and abdominal pain scores.Only a few clinical trials have found no apparent effect of probiotics on IBS symptoms.Generally,probiotics appear to be safe for patients with IBS.However,the question of which probiotics should be used for certain IBS subtypes remains unresolved.In everyday practice,the dose of the recommended probiotic remains questionable,as well as how long the probiotic should be used in therapy.The use of probiotics in the M subtype and non-classified IBS is particularly problematic,in which combination therapy should be recommended due to the change in symptoms.Therefore,new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.

Treatment of irritable bowel syndrome with multi-herbal formula: A case report

Background: Many patients with irritable bowel syndrome (IBS) try the approach of complementary or herbal medicines, as western medications do not treat IBS. The current case report presents the combine effect of four herbal components as a traditional treatment of IBS. Method: The herbal components were purchased from the local market. The components including Lipidium sativum L., Trigonella foenum-graceum L., Myristica fragrance Hoyutt. and Apium graveolens Linn were ground and mixed well (dry weight), and took orally for two days as advised by the local healer. Results: The symptoms included loose bowel movements accompanied by prolonged flatulence abdominal cramping, faecal urgency as well as mucus discharge were improved and remain suppressed for 5 to 6 months afterthe treatment with multi-herbal formula. Conclusion: The current case report showed that the multi-herbal formula might be a promising treatment for IBS-diarrhoea.

Expression of aquaporin 8 in colonic epithelium with diarrhoeapredominant irritable bowel syndrome

Background We analysed and compared the aquaporin 8 （AQP8） expression in ascending and descending colon mucosa between patients with diarrhoea-predominant irritable bowel syndrome （D-IBS） and healthy volunteers, in order to study the relationship between the clinical feature of IBS, the expression of AQP8 and the pathological mechanism of D-IBS. Methods Specimens were taken from the proximal ascending colon or distal descending colon of D-IBS patients （n=-26） and healthy volunteers （n=30）, and AQP8 mRNA expression of each specimen was determined by fluorescent quantitative reverse transcription polymerase chain reaction （FQ-RT-PCR）. In patients with D-IBS, the relationship was analysed between AQP8 expression in both ascending and descending colons and clinical features including gender, age of onset, duration of illness, frequency of defecation, and stool characteristics. Results Although AQP8 was present in the epithelium of the ascending and descending colons in healthy persons and D-IBS patients, the AQP8 level of the D-IBS patients was significantly lower than that of the healthy persons （P〈0.01 in the ascending colon, P〈0.05 in the descending colon）. AQP8 expression was not correlated with the age of patients with D-IBS （P〉0.05 both in the ascending and descending colons） or the age at the onset （P〉0.05 both in the ascending and descending colons）, but closely with the duration of illness （P〈0.05 in the ascending colon, P〈0.01 in the descending colon）, frequency of defecation （P〈0.01 in the ascending colon, P〈0.05 in the descending colon） and stool characteristics （P〈0.01 in the ascending colon, P〉0.05 in the descending colon）. Conclusions The decreased AQP8 expression in D-IBS patients indicates that dysfunction of colonic absorption may cause reduced water absorption, loose stool and diarrhoea. The expression of AQP8 may be related to D-IBS.

Post-marketing Re-evaluation of Tongxiening Granules (痛泻宁颗粒) in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome:A Multi-center,Randomized,Double-Blind,Double-Dummy and Positive Control Trial

Objective: To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea(IBS-D). Methods: A randomized, double-blind, double-dummy, and positive paral el control ed clinical trial was conducted from October 2014 to March 2016. Total y 342 patients from 13 clinical centers were enrolled and randomly assigned(at the ratio of 1:1) to a treatment group(171 cases) and a control group(171 cases) by a random coding table. The patients in the treatment group were administered oral y with TXNG(5 g per time) combined with pinaverium bromide Tablet simulator(50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator(5 g per time) combined with pinaverium bromide Tablets(50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score(IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief(AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire(IBS-QOL), Hamilton Anxiety Scale(HAMA), Hamilton Depression Scale(HAMD), and the recurrence rate at fol ow-ups. Safety indices including the adverse events(AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set(FAS) and per protocol set(PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group(147/171, 86.0%) was higher than the control group(143/171, 83.6%) by FAS(P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups(P>0.05). The recurrence rate at 8-week fol ow-up was 12.35%(10/18) in treatment group and 15.79%(12/76) in control group, respectivery(P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups(P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide.(No. ChiCTR-IPR-15006415)

Clinical Evaluation of Soothing Gan(肝) and Invigorating Pi(脾)Acupuncture Treatment on Diarrhea-predominant Irritable Bowel Syndrome

Objective： To explore the effect of Soothing Gan （肝） and invigorating Pi （脾） （SGIP） acupuncture treatment on the clinical symptoms and quality of life （QOL） in patients with diarrhea-predominant irritable bowel syndrome （IBS-D）. Methods： With a single-blinded randomized control study adopted, 63 patients who met the inclusion criteria were assigned by a random number table to two groups, 31 in the treatment group and 32 in the drug control group. The treatment group received SGIP acupuncture therapy; while the control group was treated orally with pinaverium bromide. The treatment duration of both groups was 28 days. The clinical efficacy was evaluated and compared by scoring patient＇s symptom and QOL. Results： A significant difference was found by variance analysis in efficacies between the two groups （P〈0.01）, shown as the quicker initiation of effect （P〈0.05） and the more evident clinical improvement in symptoms along the increase in treatment duration, as well as the more significant elevation of QOL in the acupuncture treatment group （P〈0.01）. SGIP displayed its superiority especially in improving dysphoria, conflict behavior, dietary restrictions, and social responses. Conclusion： SGIP acupuncture treatment could effectively alleviate the degree and frequency of symptoms＇ attack in IBS-D patients, such as abdominal pain, diarrhea, abdominal distension, etc., markedly relieve the tenesmic sensation, with the efficacy better than that of pinaverium bromide, showing a preponderance in improving patient＇s QOL.

Effect of Tongxie Yaofang(痛泻要方) Granule in Treating Diarrhea-Predominate Irritable Bowel Syndrome

Objective:To study the clinical effect of Tongxie Yaofang(痛泻要方,TXYF) Granule in treating diarrhea-predominate irritable bowel syndrome(D-IBS) and its possible mechanism.Methods:A total of 120 patients were assigned to two groups using stratified block randomization,80 in the intervention group and 40 in the control group.To the intervention group the TXYF granule was given at one package each time,twice a day; the control group was treated with Miyarisan three times a day,two tablets each time.The course of...

肠激安胶囊对IBS-D模型大鼠脑肠轴中NPY mRNA表达及ACTH含量的影响

目的探讨肠激安胶囊对腹泻型肠易激综合征(diarrhea predominant irritable bowel syndrome,IBS-D)大鼠下丘脑和结肠组织神经肽Y(neuropeptide Y,NPY)mRNA表达和血清促肾上腺皮质激素(adreno-cortico-tropic hormone,ACTH)含量的影响。方法将SD大鼠随机分为正常组,模型组,匹维溴铵组(0.018g/kg),肠激安胶囊高(2.812g/kg)、中(1.406g/kg)、低(0.703g/kg)剂量组,每组8只,模型组以及给药组采用母乳分离+醋酸刺激+四肢束缚法制备IBS-D大鼠模型,正常组和模型组给予生理盐水,给药组灌胃14天,采用ELISA法检测各组大鼠血清ACTH含量,采用RT-PCR法检测各组大鼠下丘脑及结肠组织NPYmRNA表达。结果与正常组比较,模型对照组大鼠血ACTH明显升高(P<0.01),下丘脑、结肠组织NPYmRNA表达明显降低(P<0.01);与模型组比较,肠激安胶囊高、中剂量组及匹维溴胺组大鼠血ACTH明显降低(P<0.01,P<0.05),匹维溴铵组和肠激安胶囊高、中、低剂量组下丘脑、结肠组织NPYmRNA表达上调(P<0.05)。结论肠激安胶囊对IBS-D大鼠脑肠轴异常有调节作用,其作用机制可能是通过上调下丘脑和结肠组织NPYmRNA表达和下调HPA轴中ACTH含量。

针刺疗法调节IBS-D大鼠肠道菌群结构和促进肠紧密连接的作用研究

【目的】探讨针刺改变肠道菌群结构及促进肠紧密连接对腹泻型肠易激综合征(IBS-D)大鼠的作用机制。【方法】将48只Wistar大鼠随机分为4组,即正常组、模型组、西药组和针刺组,每组各12只。通过强行应激法(CAS)刺激构建IBS-D大鼠模型,西药组予匹维溴铵混悬液灌胃,每日15 mg/kg;针刺组双侧取穴:ST25(天枢),SP15(大横),ST36(足三里),ST37(上巨虚),LR3(太冲)以及GV20(百会),针刺深度3 mm,留针20 min,每隔5 min行针1次;正常组、模型组、针刺组每日灌服生理盐水;正常组、模型组、西药组每日予同针刺组相同固定束缚时间。以上处理方法,1次/d,连续干预14 d。观察各组大鼠排便和腹泻的情况,并行粪便16 s测序分析大鼠肠道菌群变化,结肠组织行Real-time PCR法和免疫组化法检测紧密连接蛋白ZO-1、Occludin基因表达量。【结果】与模型组比较,针刺组腹泻症状改善,菌群多样性升高(P<0.05),乳酸杆菌科(Lactobacillaceae)和双歧杆菌科(Bifidobacteriaceae)丰度上升(P<0.01),结肠紧密连接基因ZO-1和Occludin表达量显著升高(P<0.01),差异菌群与紧密连接蛋白表达呈正相关。【结论】针刺可调节IBS-D肠道菌群结构,增加菌群多样性及上调肠屏障相关益生菌丰度,并介导ZO-1和Occludin的表达。

IBS-D患者直肠乙状结肠交界黏膜MC活化及类胰蛋白酶的变化及作用研究

目的研究MC的活化及类胰蛋白酶在IBS-D中的发病机制中所起到的作用。方法选择满足RomeⅢ诊断标准的IBS-D患者20例,健康的志愿者10例。应用免疫组化方法对肠黏膜MC染色,计算每高倍视野下MC的数量及活化MC占MC总数的比例,并与IBS-D患者GSRS进行相关性分析。结果 IBS-D患者MC数量与正常对照组对比差异有统计学意义(P<0.05);且其活化MC比率显著高于正常对照组(P<0.01)。IBS-D患者活化MC胞质增多,胞质染色呈深褐色,并可见脱颗粒现象。MC细胞活化分数与GSRS呈正相关(r=0.626,P=0.003)。结论 IBS-D患者MC数量明显增加及活化,与其发病机制密切相关,类胰蛋白酶在IBS-D中可能起着关键作用。

腹部推拿调控Tryptase-PAR2-PKCε通路防治IBS-D内脏痛的机制研究

[目的]验证腹部推拿防治腹泻型肠易激综合征(IBS-D)模型大鼠内脏高敏感的效果,阐明其作用途径与机制。[方法]40只SD雄性大鼠,随机分为空白组、模型组、腹部推拿组、西药组,每组10只。采用母婴分离结合慢性应激法制备IBS-D大鼠模型。应用腹壁撤退评分评价干预效果。采用甲苯胺蓝染色观察结肠组织肥大细胞(MC)聚集数量及状态。利用免疫组化及蛋白质印迹法(Western blot)法分别检测胰蛋白酶(Tryptase)颗粒分布、结肠组织中蛋白酶激活受体2(PAR2)和蛋白激酶Cε(PKCε)蛋白表达。[结果]与模型组比较,腹部推拿组和西药组腹壁撤退反射评分(AWR)明显降低(P<0.05)。镜下显示,模型组MC形态不规则,计数及密度显著高于空白组;腹部推拿组、西药组与模型组相比,MC计数降低、密度减少(P<0.01)。免疫组化检测发现与模型组相比,腹部推拿组、西药组MC Tryptase颗粒分布明显降低(P<0.01);Western blot检测发现与模型组相比,腹部推拿组和西药组的PAR2、PKCε表达量均显著降低(P<0.01)。[结论]腹部推拿作用于腹部,可能通过活化肠道MC,调控其脱颗粒,降低Tryptase释放,并借助Tryptase-PAR2-PKCε通路,进而改善IBS-D模型大鼠肠道高敏感性作用机制。

固肠胶囊联合双歧杆菌四联活菌片治疗IBS-D疗效及对患者肠道菌群、肠黏膜屏障功能的影响

目的:探究固肠胶囊联合双歧杆菌四联活菌片治疗腹泻型肠易激综合征(IBS-D)的临床疗效及对患者肠道菌群、肠黏膜屏障功能的影响。方法:IBS-D患者86例随机分为对照组(n=39)和观察组(n=47)。对照组给予双歧杆菌四联活菌片口服治疗,观察组在对照组治疗基础上给予固肠胶囊口服治疗,疗程均为1个月。评价两组患者症状改善及临床疗效,评估排便症状及大便性质改善有效率;检测两组患者治疗前后肠道肠杆菌、肠球菌、双歧杆菌、乳杆菌及酵母样真菌菌落数量及血清中肠黏膜屏障功能相关因子D-乳酸(D-LA)、肿瘤坏死因子-α(TNF-α)及乳脂球表皮生长因子-8(MFG-E8)含量。结果:观察组IBS症状尺度表总体疗效、大便性质改善的效果与对照组有差别(P<0.05)。治疗后,观察组患者腹痛程度、腹痛天数、腹胀程度、排便满意度、生活干扰度、IBS-BSS、每日排便次数、10 d中排便急迫天数均较治疗前降低(P<0.05),且优于对照组(P<0.05);与治疗前比较,观察组患者肠道肠杆菌、酵母样真菌菌落数量降低,肠球菌、双歧杆菌、乳杆菌菌落数量增加,血清D-LA、TNF-α含量下降,MFG-E8含量升高(P<0.05);且上述指标均有与对照组治疗后。结论:固肠胶囊联合双歧杆菌四联活菌片治疗IBS-D有较好的临床疗效,其作用机制与改善肠道菌群、增强肠黏膜屏障功能有关。

不同产地乌药质量评价及其改善IBS-D大鼠肠道低度炎症的机制研究

目的基于高效液相色谱法(high performance liquid chromatography,HPLC)对10批次不同产地乌药进行质量评价,并进一步探究乌药对腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome,IBS-D)大鼠肠道低度炎症的作用机制。方法采用HPLC对10个不同批次乌药进行质量评价。选取雄性SD大鼠60只,随机分为对照组、IBS-D模型组、乌药低剂量组、乌药中剂量组、乌药高剂量组、阳性药物组。除对照组外,其余大鼠均接受“番泻叶灌胃联合束缚应激”刺激,构建IBS-D大鼠模型。乌药低、中、高剂量组大鼠分别灌胃乌药水提物(0.94、1.88、3.76 g·kg-1),阳性药物组大鼠予以匹维溴铵片水溶液(1.5 g·kg-1);而对照组和IBS-D模型组大鼠灌胃等体积蒸馏水,共计2周;采用HE染色、PAS染色观察大鼠结肠变化;运用免疫组织化学法和Western blot技术检测大鼠结肠组织中过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPAR-γ)、血管细胞黏附分子1(vascular cell adhesion molecular-1,VCAM-1)、原癌基因酪氨酸蛋白激酶(proto-oncogene tyrosine-protein kinase Src,SRC)、Yes相关蛋白(Yes-associated protein,YAP)蛋白的相对表达水平。结果相似度评价、聚类结果和主成分分析结果显示,除浙江乌药(S6)外,其余批次乌药质量从整体上而言稳定可靠。HE染色和PAS染色结果显示,与对照组相比,IBS-D模型组大鼠结肠隐窝深度明显变浅、隐窝处杯状细胞数量明显减少;与IBS-D模型组相比,中、高剂量的乌药水提物能明显改善IBS-D大鼠结肠组织隐窝深度变浅及杯状细胞减少的状态;免疫组织化学和Western blot结果显示,3个剂量组的乌药水提物均可显著增强IBS-D大鼠结肠中PPAR-γ、YAP和SRC蛋白的相对表达量(P<0.05),同时能显著降低VCAM-1蛋白的相对表达量(P<0.05)。结论不同批次的乌药化学成分和含量差异不大,乌药能显著改善IBS-D大鼠低度炎症,其作用机制可能与调控PPAR-γ/VCAM-1有关。

调神健脾针法治疗IBS-D及对脑肠肽水平的影响

目的探讨调神健脾针法对腹泻型肠易激综合征(IBS-D)及脑肠肽水平变化的影响。方法IBS-D患者66例(脱落9例)随机分为针刺组(29例)和药物组(28例)。药物组口服匹维溴铵(50 mg/次,3次/d)+双歧杆菌乳杆菌三联活菌片(4片/次,3次/d),针刺组予调神健脾针法,1次/d,5次/周,均治疗4周。观察IBS-D临床症状积分、IBS-QOL评分及脑肠肽水平的变化。结果治疗4周后,两组脑肠肽水平均有所下降,差异无统计学意义(P>0.05)。治疗4周后及随访3个月时,对两组患者IBS-D临床症状积分与IBS-QOL评分进行两因素重复测量方差分析,治疗与时间存在交互作用(F交互=14.182,P<0.01;F交互=15.103,P<0.01),针刺组临床症状积分及IBS-QOL评分部分维度改善明显,临床疗效优于对照组(P<0.05)。结论“调神健脾”针法可明显缓解IBS-D症状,改善生活质量,可能与针刺降低脑肠肽水平、调节内脏高敏有关。

广藿香配方颗粒干预IBS-D大鼠的药效学研究

目的:观察广藿香配方颗粒对腹泻型肠易激综合征(IBS-D)大鼠的治疗作用,并探讨其作用机理。方法:采用慢性束缚应激诱导建立IBS-D大鼠模型,72只大鼠随机分为正常对照组、模型组、匹维溴铵阳性对照组及广藿香配方颗粒低、中、高剂量组,连续给药14 d,定期测定各组大鼠的内脏敏感性、排便情况,末次给药后测定结肠匀浆5-羟色胺3A受体(5-HT3AR)、5-羟色胺4受体(5-HT4R)、神经激肽受体1(NK-1R)、神经元型一氧化氮合酶(n NOS)mRNA表达水平。结果:与正常对照组比较,模型组大鼠腹壁回缩反射评分显著提高,排便显著增加(P<0.01),结肠组织5-HT3AR、5-HT4R、NK-1R mRNA表达显著升高(P<0.05),n NOS mRNA表达显著降低(P<0.01)。与模型组比较,广藿香配方颗粒可使IBS-D大鼠腹壁回缩反射评分显著降低、排便显著减少,结肠组织5-HT3AR、5-HT4R、NK-1R mRNA表达水平显著降低,n NOS mRNA表达水平显著升高(P<0.05或P<0.01),对IBS-D大鼠有明显的治疗作用。结论:广藿香配方颗粒可改善慢性束缚应激IBS-D模型大鼠的内脏高敏感性和排便情况,其作用机制可能与调节大鼠结肠5-HT3AR、5-HT4R、NK-1R、n NOS mRNA表达水平有关。