枯草杆菌屎肠球菌二联活菌制剂对急性肝衰竭大鼠肠道微生态失调的调节作用

目的:探讨枯草杆菌屎肠球菌二联活菌制剂(商品名:美常安)对急性肝衰竭(AHF)大鼠肠道微生态失调的调节作用。方法:用D-氨基半乳糖(D-gal)1.2 g/kg腹腔注射制成AHF模型。将实验动物分为对照组、模型组、治疗组,分别检测肠道菌群变化和内毒素含量。结果:经过美常安治疗2周后,大鼠肠道内有益菌含量明显上升,有害菌含量下降,肠道菌群比例恢复正常,血中内毒素含量降低。结论:美常安通过对AHF大鼠肠道微生态失调的直接调节作用,间接的起到了保肝护肝的作用,对于AHF疾病的本身也起到了积极的治疗作用。     

桦褐孔菌多糖对溃疡性结肠炎大鼠模型血清IL-6、IL-10的调节作用

目的：观察桦褐孔菌多糖对2、4、6-三硝基苯磺酸（rNBS）诱导的溃疡性结肠炎大鼠模型血清IL-6、IL-10的调节作用.方法：TNBS灌肠制备溃疡性结肠炎大鼠模型,造摸成功后用桦褐孔菌多糖灌胃治疗,14天后测大鼠血清内IL-6、IL-10的水平.结果：与模型组相比,IL-6含量明显降低（P＜0.05）;IL-10含量明显升高（P＜0.05）.结论：桦褐孔菌多糖可通过调节血清中细胞因子IL-6和IL-10在体内的水平,通过提高溃疡性结肠炎大鼠模型的免疫功能而达到治疗的作用.     

肠康宁对溃疡性结肠炎大鼠IL-2、IL-4的实验研究

目的观察肠康宁对溃疡性结肠炎大鼠IL-2、IL-4的影响。方法采用三硝基苯磺酸/乙醇联合造模法制备大鼠溃疡性结肠炎模型,随机分为空白组、模型组、柳氮磺胺吡啶组、肠康宁高、低剂量组,采用ELISA法测定血清中IL-2、IL-4的含量。结果肠康宁各组可使血清中IL-2水平明显降低,IL-4水平明显提高。结论肠康宁对溃疡性结肠炎大鼠有良好的治疗作用,其作用机制可能是与抑制IL-2,提高IL-4有关。     

雷公藤多甙对溃疡性结肠炎大鼠模型TNF-α和ICAM-1的影响

目的 探讨雷公藤多甙对大鼠溃疡性结肠炎炎性损伤的保护作用及可能机制。方法 采用三硝基苯磺酸（TNBS）制备大鼠溃疡性结肠炎模型，将动物随机分为正常对照组、模型组、生理盐水组及雷公藤多甙组4组。采用免疫组织化学染色检测肠组织TNF-α和ICAM-1表达，生化方法检测SOD、MDA和MPO含量，并观察肠道人体形态和组织学改变。结果溃疡性结肠炎模型组TNF-α、ICAM-1表达及MDA、MPO含量较正常组及生理盐水组显著增高，而SOD活性明显降低（P〈0．01），雷公藤多甙组TNF-α、ICAM-1表达，MDA、MPO含量明显低于溃疡性结肠炎模型组，SOD活性显著高于模型组（P〈0．01），雷公藤多甙组结肠炎性损伤评分指数叫显降低（P〈0．01）。结论 雷公藤对溃疡性结肠炎具有良好的保护作用，抗氧化及抑制炎性因子浸润可能是其主要的作用机制之一。     

结直肠癌患者术后肠道菌群变化及微生态制剂治疗效果研究

目的:探讨结直肠手术对结直肠癌患者肠道菌群的影响及微生态制剂治疗肠道菌群失调的效果.方法:选择50例结直肠癌择期手术患者随机分为微生态组和对照组各25例,术后对照组常规处理,微生态组给予三联活菌制剂口服治疗,采用细菌DNA PCR分析定量肠道细菌量,检测血浆D-乳酸和尿L/M水平,对比手术前后肠道菌群变化和肠道屏障功能.结果:术后10天双歧杆菌、乳酸杆菌显著降低,而微生态组显著高于对照组,大肠杆菌、粪肠球菌显著升高,微生态组显著低于对照组,B/E呈显著倒置,对照组倒置更为显著(P值＜0.05);术后60天,微生态组双歧杆菌、乳酸杆菌、大肠杆菌、粪肠球菌量及B/E基本恢复术前水平,而对照组仍显著低于术前(P值＜0.05).术后1天血浆D-乳酸和尿L/M水平显著升高(P值＜0.05),术后10天两组血浆D-乳酸和尿L/M水平均回落,微生态组回落较对照组显著且显著低于对照组(P值＜0.05).结论:结直肠癌术后患者肠道内双歧杆菌、乳酸杆菌等益生菌显著减少,大肠杆菌和粪肠球菌显著增加,肠道菌群严重失调,肠道屏障功能受损,微生态制剂治疗有助重建肠道菌群平衡,恢复肠道屏障功能.     

091 微生态制剂用于急性重症胰腺炎病人的营养治疗

急性重症胰腺炎是临床较为常见的危急重症,而继发感染是急性胰腺炎患者死亡的最主要原因,目前普遍认为肠内细菌易位是导致胰腺感染的主要因素.应用微生态制剂调整肠内菌群构成,增加肠粘膜屏障作用是防治内源性感染有效而可行的方法.本文综述了用微生态制剂肠内营养治疗急性重症胰腺炎病人的研究进展.     

微生态制剂用于急性重症胰腺炎病人的营养治疗

急性重症胰腺炎是临床较为常见的危急重症，而继发感染是急性胰腺炎患死亡的最主要原因，目前普遍认为肠内细菌易位是导致胰腺感染的主要因素。应用微生态制剂调整肠内菌群构成，增加肠粘膜屏障作用是防治内源性感染有效而可行的方法。本综述了用微生态制剂肠内营养治疗急性重症胰腺炎病人的研究进展。     

艾司洛尔对脓毒症大鼠肠黏膜屏障的影响

目的:探讨艾司洛尔对脓毒症大鼠肠黏膜屏障的保护作用. 方法:建立脓毒症大鼠模型,将大鼠随机分为对照组(脓毒症组)和艾司洛尔组(脓毒症模型+艾司洛尔组),每组8只.观察大鼠的基本生命体征、体外肠道的通透性和血清内毒素变化.同时,通过肝、脾和肠系膜淋巴结细菌培养观察细菌易位情况.最后,根据H-E染色结果评估大鼠肠道损伤. 结果:艾司洛尔组大鼠心率明显低于基础值(P＜0.05).与对照组比,艾司洛尔组大鼠细菌易位减少,体外肠道通透性降低.两组大鼠血清内毒素水平无显著性差异.艾司洛尔组大鼠肠道病理评分明显低于对照组. 结论:艾司洛尔能保护脓毒症大鼠肠黏膜屏障,减轻肠损伤.     

丹参对实验性大鼠溃疡性结肠炎预防机制研究

目的研究丹参对大鼠溃疡性结肠炎（UC）预防机制。方法予雌性Sprague-Dawley大鼠含30 mg三硝基苯磺酸（TNBS）的50%乙醇溶液0.85 ml灌肠,诱导实验性溃疡性结肠炎。丹参预防组,造模前先用丹参从尾静脉注入丹参注射液2 ml.kg-1.d-1连续3 d。造模7 d后,正常对照组、丹参预防组和造模组尾静脉注入0.9%NaCl溶液1 ml/d;丹参治疗组每天尾静脉注入丹参注射液2 ml.kg-1.d-1。通过肠道重量指数、溃疡面积、大体形态和组织学评分及血和肠黏膜中一氧化氮（NO）、超氧化歧化酶（SOD）含量测定评估疗效。结果丹参预防组肠道重量指数、溃疡面积、大体形态和组织学评分及血和肠黏膜中NO含量减少、SOD含量增高,与丹参治疗组、模型组比较差异有统计学意义（P〈0.01）;但较正常对照组NO含量仍增高和SOD含量减少。结论丹参有效预防大鼠UC发生和发展,可能丹参具有拮抗NO、氧自由基机制有关。     

益生菌对急性胰腺炎大鼠肠道微生态及紧密连接的影响

目的 探讨经肠道补充益生菌对急性胰腺炎（AP）大鼠肠上皮细胞紧密连接、屏障功能及微生态的影响.方法 经胰管注射3%牛磺胆酸钠造成大鼠AP后,分别给予肠外营养（PN组）和PN＋益生菌（益生菌组）,持续5天;第6天处死大鼠,取腔静脉血、肺及肝组织和肠系膜淋巴结匀浆作细菌培养测细菌易位率;取末段回肠和结肠,采用免疫组织化学法测定其跨膜结合蛋白表达,电镜观察肠上皮细胞紧密连接超微结构;取盲肠内粪便作厌氧培养及细菌种群DNA指纹图谱分析.结果 益生菌组大鼠肠道内乳杆菌和双歧杆菌数量高于PN组（P＜0.05）,而潜在致病菌产气荚膜梭菌低于PN组（P＜0.05）,DNA指纹图谱也显示益生菌组优势菌群的基因条带和正常大鼠具有较高一致性,与PN组相比则有明显差异;益生菌组小肠和大肠跨膜结合蛋白的表达明显优于PN组（P=0.001,P=0.036）,肠上皮细胞紧密连接、微绒毛较完整;益生菌组大鼠的血、肺、肝、肠系膜淋巴组织的细菌易位率低于PN组（P=0.0413）.结论 益生菌能纠正AP大鼠PN时肠道菌群紊乱,增加肠上皮跨膜结合蛋白表达,维持肠上皮紧密连接,减少细菌易位。     

A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8) colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.     

Pretreatment and Treatment With L‐Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis

Background: Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. Methods: C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L ‐arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L ‐arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). Results: The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine‐supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Conclusions: Arginine attenuates weight loss and BT in mice with colitis.     

黄芪多糖对心肌缺血再灌注损伤大鼠的保护作用

目的 研究黄芪多糖是否对心肌缺血再灌注损伤大鼠具有保护作用。方法 SD大鼠随机分为假手术组,心肌缺血再灌注组、黄芪多糖低、中、高剂量预处理组（n=10）。不同剂量药物干预10d后,利用结扎大鼠冠状动脉左前降支的方法建立心肌缺血再灌注损伤模型,之后采集大鼠血清测定其中乳酸脱氢酶、肌酸激酶、肌酸激酶同工酶、天门冬氨酸氨基转移酶和α-羟丁酸脱氢酶的含量。并对大鼠左心室组织进行HE染色。以上述5项心肌酶含量及分析心肌细胞形态学的方法评价黄芪多糖的效果。结果 黄芪多糖预处理组与假手术组相比并可使心肌酶指标有所降低,差异具有统计学意义（P＜0.05）。从形态学分析,黄芪多糖预处理组还能改善因缺血再灌注损伤的心肌组织。结论 黄芪多糖能在一定程度上逆转心肌缺血再灌注大鼠被损伤的心肌。     

Activation of Free Fatty Acid Receptor 4 Affects Intestinal Inflammation and Improves Colon Permeability in Mice

Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), {"type":"entrez-nucleotide","attrs":{"text":"AR420626","term_id":"40175736"}}AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacological intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation.     

大黄和早期肠内营养对肠缺血-再灌注损伤大鼠肠屏障功能的影响

目的:观察大黄和早期肠内营养(EEN)对大鼠肠缺血-再灌注损伤(IRI)后肠黏膜屏障的影响.方法:将32只大鼠随机分为对照组、EN组、大黄组、大黄+EN组.在大鼠肠IRI模型上观察再灌注24h后肠黏膜形态学的变化、血清内毒素和细菌易位指标. 结果:肠IRI可导致肠黏膜发生严重损伤.肠IRI后24h,大黄组大鼠内毒素水平...     

Effect of the administration of fermentable and non-fermentable dietary fibre on intestinal bacterial translocation in ascitic cirrhotic rats

BACKGROUND: Bacterial infections are frequent in cirrhosis. Experimental studies suggest a pathogenic role of intestinal bacterial translocation in them. Both fermentable and non-fermentable fibre avoided intestinal bacterial translocation (IBT) in animal models of gut starvation and critical illness. AIM: To assess the effect of fermentable (pectin) or non-fermentable (lignin) fibre on IBT in ascitic cirrhotic rats. METHODS: Thirty-six rats induced to cirrhosis with oral CCl4 were randomized (6 weeks after the first CCl4 dose) to receive rat chow+5% lignin (LIG, n=13), rat chow+5% pectin (PEC, n=13), or rat chow only (CON, n=10). Once ascites developed, animals were laparotomized and samples of mesenteric lymph nodes (MLN), ascitic fluid, portal and peripheral blood and liver, were obtained for culture. RESULTS: IBT rate was: LIG=5/13, PEC=4/13, CON=5/10 (P=N.S.). The median amount of translocated bacteria in rats with IBT was lower in the PEC group (2 x 10(2) CFU/g MLN), than in LIG (10(5) CFU/g MLN) and CON (10(4) CFU/g MLN) groups (P<0.05). All other samples were sterile except for a portal blood sample (Enterococcus faecalis) of the LIG group. CONCLUSIONS: IBT incidence is not decreased by either pectin or lignin in ascitic cirrhotic rats, but pectin supplementation reduces the amount of translocated bacteria.     

小檗碱治疗大鼠免疫复合性溃疡性结肠炎及下调炎性细胞因子作用

目的探讨小檗碱(berberine,BER)对免疫复合性溃疡性结肠炎模型大鼠的作用及其与细胞因子的关系。方法健康SD大鼠64只,雌雄各半,随机分为正常对照组(12只)和模型组(52只);模型组应用免疫复合法(注射抗原乳化剂+TNBS/乙醇)建立溃疡性结肠炎大鼠模型,正常组注射生理盐水。再喂养3周后,随机从造模组中抽取4只处死,检查结肠病变情况,确定溃疡性结肠炎模型建立;随后将造模大鼠随机分为4组:BER低剂量组(0.1 g·kg-1),BER高剂量组(0.2 g·kg-1),柳氮磺吡啶(SASP)组(0.1 g·kg-1)和模型对照组;每组12只,每天灌胃给药1次,连续给药4周。每周观察大鼠疾病活动指数(DAI);末次给药后,处死动物,解剖观察并评定结肠黏膜损伤指数(CMDI);石蜡切片,HE染色,光镜下观察结肠组织的病理学变化,并做组织病理变化评分(HS);采用酶联免疫吸附剂测定(ELISA)方法测定血清IL-6、IL-8、IL-17、TNF-α水平变化。结果模型大鼠的DAI,CMDI,结肠HS评分均明显上升(P<0.01);血清中的IL-6、IL-8、IL-17、TNF-α含量明显上升(P<0.01);BER治疗4周后,使模型大鼠的DAI、CMDI、结肠HS评分均能显著下降(P<0.01),同时降低血清中IL-6、IL-8、IL-17、TNF-α的浓度(P<0.01)。结论 BER对免疫复合法诱致溃疡性结肠炎模型大鼠具有治疗作用,其机制可能与降低血清中IL-6、IL-8、IL-17、TNF-α含量及调节体内免疫反应有关。     

应用绿色荧光蛋白标记技术示踪细菌移位的实验研究

目的:利用绿色荧光蛋白(GFP)标记技术明确化疗时是否存在细菌移位.方法:将30只SD大鼠随机分为三组:空白对照组、对照组和甲氨蝶呤(MTX)组,每组10只.给对照组和MTX组大鼠灌饲GFP标记的大肠杆菌TG1对移位的细菌进行示踪,MTX组大鼠皮下注射MTX制作大鼠化疗模型.使用荧光显微镜及质粒酶切电泳鉴定内脏分离出的细菌是否来源于肠道.结果:在应用MTX大鼠的肠系膜淋巴结、肝、脾和肾,均可分离出GFP标记E.coli TG1.结论:MTX能引起细菌移位,在细菌移位的动物实验研究中,GFP示踪技术是一种简单、可靠和有效的方法.     

Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis

BACKGROUND: Alterations of intestinal flora, such as reduction in the concentration of bifidobacteria and increase in that of Bacteroides species, are apparently associated with the severity of ulcerative colitis. OBJECTIVE: We conducted a randomised clinical trial of the use of a bifidobacteria-fermented milk (BFM) supplement as a dietary adjunct in the treatment of ulcerative colitis. METHODS: The subjects were randomly divided into two groups: a group with BFM supplementation (BFM group, 11 subjects) and a control group (control group, 10 subjects). The BFM group was given 100 mL/day of BFM for one year. Colonoscopies, general blood markers and examinations of intestinal flora including the analysis of fecal organic acids were performed at the commencement of the study and after one year. RESULTS: Exacerbation of symptoms was seen in 3 out of 11 subjects in the BFM group and in 9 out of 10 in the control group. Log rank statistic analysis of the cumulative exacerbation rates showed a significant reduction in exacerbations for the BFM group (p = 0.0184). The analysis of microflora and the organic acids in the feces showed a significant reduction in the relative proportion of B. vulgatus in Bacteroidaceae and butyrate concentration, respectively, after supplementation with BFM, in comparison with before. CONCLUSION: Supplementation with the BFM product was successful in maintaining remission and had possible preventive effects on the relapse of ulcerative colitis.     

溃疡性结肠炎患者炎性因子水平、肠道菌群分布及发病相关因素分析

目的研究溃疡性结肠炎患者的炎性因子水平、肠道菌群分布及发病相关危险因素,为溃疡性结肠炎的防治工作提供科学依据。方法以2020年6月至2021年5月在文昌市某医院就诊的溃疡性结肠炎患者作为病例组,同时选取(按年龄相差0.5岁,性别相同招揽志愿者参与本研究)同期在该医院进行健康体检者作为对照组。所有研究对象进行问卷调查、肠道菌群检测及炎症因子检测,采用描述性分析方法对2组相关指标进行比较,并对溃疡性结肠炎发病影响因素进行单、多因素分析。结果共纳入溃疡性结肠炎病例(病例组)和健康体检者(对照组)各200例,男性各99例,女性各101例,病例组平均年龄(43.17±8.72)岁,对照组平均年龄(43.54±9.11)岁,2组的年龄、性别分布差异均无统计学意义(均P>0.05)。病例组主要检出的双歧杆菌、乳杆菌数量低于对照组,拟杆菌、肠杆菌、肠球菌、梭杆菌数量高于对照组(均P<0.01)。病例组除白细胞介素(IL)-4水平低于对照组,IL-6、IL-17、IL-23以及肿瘤坏死因子-α(TNF-α)均高于对照组(均P<0.01)。饮酒(OR=3.526)、吸烟(OR=1.272)、饮食不洁(OR=4.592)、存在合并感染(OR=2.146)、情绪紧张(OR=3.919)均为溃疡性结肠炎发病的危险因素。结论溃疡性结肠炎患者肠道菌群种类、数量分布不平衡,血清炎症因子水平明显上升。良好的生活行为习惯以及积极地健康教育可降低溃疡性结肠炎的发生风险。