内皮素在梗阻性黄疸肝、肾、心组织损伤中的作用及血塞通干预

目的 探讨内皮素（ET）在梗阻性黄疸肝、肾、心组织损伤中的作用机理及血塞通注射液的保护作用。方法 健康日本大耳白兔72只，雌雄各半，采用完全随机分组方法随机均分为3组：胆总管结扎（BDL）组、BDL＋血塞通注射液组及假手术组。建立实验动物模型，分别于术后3、6、9及21d取材。用全自动生化分析仪测定各组动物血清总胆红素、谷丙转氨酶、尿素氮及肌酐；用放免法测定各组动物肝、肾、心组织及血浆中的ET水平。结果 BDL组和BDL＋血塞通注射液组与假手术组比较，动物血浆及肝、肾、心组织中的ET含量明显升高（P〈0．01），肝、肾功能损害更严重（P〈0．01）；BDL＋血塞通注射液组比BDL组血浆及组织中ET含量明显降低（P〈0．05），肝、肾功能损害亦减轻（P〈0．05）。结论梗阻性黄疸可导致血浆及肝、肾、心组织ET含量升高，且随梗阻时间延长升高愈明显；血塞通注射液通过降低血浆及组织的ET水平，发挥对梗阻性黄疸肝、肾、心损害的保护作用。     

L-精氨酸对阻塞性黄疸大鼠单核吞噬细胞系统功能的影响

目的：探讨L－精氨酸（L－Arg)对阻塞性黄疸大鼠单核吞噬细胞系统（MPS）吞噬功能的影响。方法：将SD雄性大鼠54只随机分为3组：假手术对照组（SO）;胆总管结扎组（BDL）;胆总管结扎＋L－精氨酸组（BDL＋L－Arg),每组术后又分设7,14,21d3个时间点检测MPS和枯否细胞（KC）的吞噬功能,并测定肝组织丙二醛（MDA）和NO2^-/NO3^-含量。结果：与SO组比较,BDL组各时间点MPS吞噬功能（P＜0．01）和KC吞噬功能（P＜0．05）明显减弱。BDL＋L－Arg组在胆管结扎7,14d时MPS和KC吞噬功能明显强于BDL组（P＜0．05）,21d时两组MPS和KC吞噬功能差异无显著性（P＞0．05）,但与SO组相比,BDL＋L－Arg组各时间点MPS吞噬功能仍明显降低（P＜0．05）。BDL L-Arg组在胆管结扎7,14d时血清转氨酶和肝组织MDA含量显著低于BDL组（P＜0．05）,而NO2^-/NO3^-含量显著高于BDL组（P＜0．01）。结论：L－精氨酸有减轻阻塞性黄疸时肝脏损伤和增强MPS,KC吞噬功能的作用,但存在一定时效关系。     

急性坏死性胰腺炎大鼠肠道黏膜屏障功能的损害及肠道细菌移位

目的观察急性坏死性胰腺炎（ANP）时肠道黏膜屏障的变化和肠道细菌移位。方法选择SD大鼠，逆行胰胆管穿刺法诱导制备大鼠ANP模型并分为两组，分别为假手术组（SO）和坏死组（ANP）。术后24h，观察大鼠ANP模型的回肠黏膜通透性、回肠绒毛高度和黏膜厚度的变化，测定血浆D-乳酸浓度和血浆内毒素水平，并行脏器细菌培养。结果ANP组血浆内毒素水平较SO组升高（P〈0．01），细菌培养SO组均无阳性，ANP组细菌培养总阳性率为55．6％，其中以腹水细菌培养阳性率最高，为75．0％，菌种鉴定主要为肠球菌和变形杆菌。ANP组24h后血浆D-乳酸浓度高于SO组，差异有统计学意义（P〈0.01）。ANP组24h回肠黏膜发生病理形态学的改变，从绒毛高度和黏膜厚度测量值上观察发现ANP组肠壁明显变薄。结论本组实验中，大鼠ANP时的回肠黏膜病理形态学的变化提示ANP大鼠肠道的机械屏障明显受损；血浆D-乳酸浓度的显著上升，证明它可从功能上反映ANP大鼠肠道屏障功能的损害。大鼠ANP时的内毒素水平和脏器细菌培养阳性率的升高，证明内毒素血症和肠道细菌移位是由于早期肠道通透性升高和肠道屏障受损所致。     

大黄素对阻塞性黄疸大鼠肝损害的保护作用

目的探讨大黄素防止肝纤维化的作用。方法用SD大鼠120只随机分为：(1)假手术+生理盐水组(SO+NS组)；(2)单纯胆总管结扎+生理盐水组(BDL+NS组)；(3)胆总管结扎+大黄素组(BDL+ED组),每组40只。BDL+NS组作胆总管结扎、生理盐水灌胃；BDL+ED组行胆总管结扎、大黄素混悬液灌胃。分别于14、21 d各处死每组大鼠的50%,观察肝纤维化情况和检测肝功能、小肠细菌移位。结果结扎胆总管大鼠的肠黏膜、肝纤维化及肝功能的受损随结扎时间延长而逐渐加重,但用大黄素组有显著减轻,结扎后21 d BDL+NS组与BDL+ED组比较,细菌移位率为(85%比50%,P＜0．05)；肝纤维化程度(按0～4级计)为[0、4、6、8、2比4、10、3、3、0只,(P＜0．01)]；肝功能：ALT[(212．4±19．2)U/L比(146．5±16．2)U/L(P＜0．01)]；AST [(709．6±39．9)U/L比(612．2±30．8)U/L(P＜0．05)]；TB[(174．4±32．2)μmol/L比(159．8±27．2)μmol/L P＜0．05)]。结论大黄素能降低阻塞性黄疸时的肠道细菌移位率,对肝功能有明显保护作用,可有效减轻梗阻性黄疸时的肝纤维化。     

人重组生长激素对梗阻性黄疸大鼠肠源性细菌/内毒素移位的影响

目的探讨人重组生长激素(rhGH)减轻梗阻性黄疸时肠源性细菌及内毒素移位的作用及机制。方法Wister大鼠42只分为3组假手术组(SO组)、胆总管结扎组(BDL组)及rhGH治疗组(rhGH组)。实验1周后检测各组肝功指标的变化及血浆内毒素水平,取肝、肾、肠系膜淋巴结等肠道外器官组织做细菌培养,电镜观察末端回肠黏膜变化。结果rhGH组多项肝功指标较BDL组明显改善,rhGH组血浆内毒素水平为(0·38±0·03)EU/ml,较BDL组的(0·65±0·04)EU/ml明显降低(P<0·01),与SO组的(0·30±0·02)EU/ml比较无显著差异(P>0·05)。BDL组肝、肾、肠系膜淋巴结中细菌移位率高于另两组,其中肠系膜淋巴结细菌移位率为64·29%,明显高于SO组及rhGH组(P<0·05),后两组之间各部位细菌检出率差别无显著性(P>0·05)。电镜显示BDL组肠黏膜上皮细胞坏死,细胞核固缩,线粒体肿胀变性,内质网明显扩张。rhGH组肠黏膜上皮改变较BDL组明显减轻,接近SO组所见。结论应用rhGH可保护梗阻性黄疸时小肠黏膜屏障功能,减少肠源性细菌/内毒素移位的发生。     

阻塞性黄疸对肠道细菌及小肠粘膜组织的影响

为探讨阻塞性黄疸（简称阻黄）对肠道细菌及粘膜组织的影响，通过建立阻黄动物模型，观察阻黄大鼠肠道细菌移位以及小肠粘膜组织学变化。结果发现：阻黄组（ＢＤＬ）术后３周厌氧性细菌移位的阳性率（４３．７５％）显著高于假性手术组（ＳＬ）（０％），Ｐ＜０．０５；组织学检查显示ＢＤＬ组肠粘膜发生了实质性损害。提示：阻黄时肠道内胆盐缺乏导致肠道常驻菌过度繁殖，肠道粘膜屏障的损害以及机体免疫功能抑制可能是促进肠道细菌移位，导致阻黄时感染易感性增高的主要原因     

大鼠门静脉高压症及梗阻性黄疸时细菌移位与黄嘌呤脱氢酶和黄嘌呤氧化酶的关系

目的探讨大鼠门静脉高压症（porta; ju[ertemsopm,PH）及梗阻性黄疸（obstructive jaundioe,OJ）时,细菌移位（bacterial translocation,BT）与黄嘌呤氧化酶（xanthine oxidase,XO）、黄嘌呤脱氢酶（xanthine dehydrogenase,XD）之间的关系。方法将雄性SD大鼠60只随机分为对照组（A组）,胆总管结扎组（B组）和门静脉缩窄组（C组）,每组20只。术后第3周取肠系膜淋巴结、脾、肝组织及门静脉、腔静脉血细菌培养,测定门静脉压力（free portal pressure,FPP）,及肠XO,XD活性水平。结果B组及C组细菌移位率明显高于对照组（P〈0．01）,对照组为12％,B组和C组分别为28％和54％;B组和C组空肠XO水平活性明显高于对照组（P〈0．01）,B组和C组门静脉压力也较对照组升高。细菌移位率与XO活性成正相关（r=0．603）。XD活性水平无显著差异。结论门静脉高压症及梗阻性黄疸时可发生细菌移位,可能与肠黏膜屏障被破坏通透性增强有关,肠壁XO水平活性增强引起肠黏膜屏障通透性增高有助于细菌移位发生。     

加味大柴胡汤加用L-精氨酸对阻黄大鼠血浆内毒素的影响

目的　探讨L 精氨酸、加味大柴胡汤及两者合用对保护阻塞性黄疸大鼠的肝功能、抑制脂质过氧化损伤、缓解内毒素血症的作用。方法　制作急性阻塞性黄疸大鼠模型 ,分为 7、14及 2 1d 3个时段 ,每个时段分为 5组 ,每组 6只大鼠。在各时相点 ,检测内毒素和NO2 -/NO3 -的含量。结果　门静脉血浆内毒素的含量 :胆管结扎 7d后 ,门静脉血浆内毒素含量BDL NS组明显高于其他组 (P <0 .0 1)。而BDL L Arg 中药组与BDL L Arg及BDL 中药组间比较差异有显著性 (P <0 .0 5 )。胆管结扎 14d ,门静脉血浆内毒素含量BDL L Arg 中药组与BDL L Arg及BDL 中药组比较差异也有显著性 (P <0 .0 5 )。但在 2 1d时段门静脉内毒素含量BDL L Arg组与BDL NS组比差异无显著性 ,而BDL 中药组及BDL L Arg 中药组门静脉内毒素含量较上述两组差异有显著性 (P <0 .0 1)。结论　在阻塞性黄疸发病早、中期 ,采用加味大柴胡汤加L Arg治疗对保护肝功能与缓解内毒素血症作用较佳     

内皮素在阻塞性黄疸早期门静脉高压症中的作用

目的初步探讨阻塞性黄疸早期门静脉高压的机制。方法将大鼠分为胆管结扎组（B）与假手术组（A），分别于术后3、7、14d比较两组的游离门静脉压力（FPP）、血浆和肝组织内皮素（ET）浓度。结果胆总管结扎7d后门静脉压力显著高于对照组；胆总管结扎后各时段ET水平均显著高于对照组；门静脉压力与血浆ET、肝组织ET呈正相关。结论阻塞性黄疸早期即有门静脉压力的升高，它可能是体内ET水平升高致肝窦阻力增加的结果。     

血管内皮素-1在梗阻性黄疸大鼠冷应激肾损害中的作用

目的　了解血浆内皮素 1 (ET 1 )在梗阻性黄疸大鼠冷应激状态下的水平及与肾功能损害的关系。方法　实验动物随机分为 4组 :①假手术 (SO)组 ;②胆总管结扎 (BDL)组 ;③胆总管结扎应激 (BS)组 ;④BS加ET抗血清 (BAS)组。采用放射免疫的方法测定各组动物的血浆ET 1含量。结果　BS组ET 1 (2 0 6 72ng/ml± 34.31ng/ml)明显高于BDL对照组 (1 68 63ng/ml± 2 6 58ng/ml) (P <0 .0 5)。血尿素氮 (BUN) (1 2 31mmol/L± 3 1 4mmol/L)和肌酐 (Cr) (71 .64mmol/L± 9.1 4mmol/L)也较BDL组升高 (P <0 .0 5) ,BUN和Cr也均下降 ,ET 1与BUN ,Cr均呈正相关 (r=0 .743,r =0 .831 )。结论　梗阻性黄疸大鼠血浆ET 1在应激状态下明显升高 ,与BUN和Cr呈正相关 ,致使梗阻性黄疸大鼠的肾功能损害加重。     

不同营养方式对肠道缺血再灌注大鼠肠屏障功能的影响

目的探讨不同营养物质及支持途径对肠道缺血再灌注大鼠肠屏障功能和细菌易位的影响。方法60只雄性SD大鼠建立肠道缺血再灌注模型,随机分成普通肠外营养组(PN),富含谷氨酰胺的肠外营养组(G-PN),普通肠内营养组(EN)及免疫增强型肠内营养组(IEN)。从术后第1天起连续营养支持7d,各组等氮、等热卡。观察肠道形态学、肠道黏膜通透性、肠道细菌易位情况和血浆内毒素水平及肠道免疫功能检测。结果PN组肠黏膜明显萎缩,其绒毛高度、黏膜厚度、隐窝深度及绒毛表面积均显著低于其他各组(P<0.05);其肠黏膜通透性及内毒素值显著高于其他各组(P<0.05),细菌易位率(100%)明显高于其他各组(G-PN组60.0%,EN组33.3%,IEN组20.0%)。PN组CD4 T淋巴细胞和IgA 浆细胞分布显著低于其他各组(P<0.01)。结论EN在维护肠黏膜屏障功能、防止细菌及内毒素易位方面优于PN。免疫增强型EN在维护肠黏膜屏障、改善肠道免疫功能、防止细菌易位方面作用优于普通EN。     

Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats

BACKGROUND: This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN: One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS: Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.     

Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice

OBJECTIVE: To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice. SUMMARY BACKGROUND DATA: Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy. METHODS: Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 microg/kg/d), V = BDL + NT (300 microg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum. RESULTS: BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well. CONCLUSIONS: Administration of BBS or NT in bile duct-ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.     

枳术汤加味对大鼠肠黏膜屏障功能的保护作用

目的 探讨中药枳术汤加味对大鼠肠黏膜屏障功能的保护作用及其机制.方法 将70只雄性大白鼠随机分为对照组(10只)、造模组(20只)术前连续7d饮水灌胃0.35ml/次,每天2次,治疗组(20只)术前连续7d中药灌胃0.35ml/次,每天2次,大剂量治疗组(20只)术前连续7d中药灌胃0.7ml/次,每天2次.大鼠按2.5ml/kg体重的剂量给予腹腔内注射5%水合氯醛进行麻醉.进腹后血管钳夹闭肠系膜上动脉,持续30min后恢复血供,使肠道发生缺血-再灌注损伤.分别在再灌注1、24h后进行以下检测:肠道细菌移位发生率;回肠黏膜病理变化;外周血浆D-乳酸浓度、二胺氧化酶浓度;回肠黏膜细胞凋亡指数.结果 缺血-再灌注1、24h后细菌移位阳性率、细菌培养阳性率和血浆D-乳酸和二胺氧化酶浓度,造模组高于对照组(P<0.05);治疗组低于造模组(P<0.05);大剂量治疗组和治疗组比较差异无统计学意义(P>0.05). 回肠膜黏重量、绒毛高度及宽度,造模组小于对照组(P<0.05);治疗组大于造模组(P<0.05);大剂量治疗组和治疗组比较差异无统计学意义.肠黏膜上皮细胞凋亡指数,造模组高于对照组(P<0.05);治疗组低于造模组(P<0.05);大剂量治疗组和治疗组比较差异无统计学意义(P>0.05). 结论中药枳术汤加味能减少肠道细菌移位,降低肠黏膜的通透性,可以保护肠黏膜屏障功能.     

Prostaglandin E1 maintains structural integrity of intestinal mucosa and prevents bacterial translocation during experimental obstructive jaundice.

The absence of bile in the gut lumen induces mucosal injury and promotes bacterial translocation (BT). Prostaglandin E (PGE) has a protective effect on the mucosal layer of the alimentary tract. We hypothesize that PGE1 may prevent BT by its beneficial action on the mucosa of the small bowel. Thirty Wistar albino rats were divided equally into 3 groups; Group 1 (control) underwent sham laparotomy, group 2 obstructive jaundice (OJ) and group 3 (OJ + PGE1) underwent common bile duct (CBD) ligation and transection. Groups 1 and 2 received; 1 mL normal saline and group 3 received 40 mg of the PGE1 analogue misoprostol dissolved in 1 mL normal saline administered by orogastric tube once daily. After 7 days, laparotomy and collection of samples for laboratory analyses were performed, including bacteriological analysis of intestine, mesenteric lymph nodes (MLNs), and blood, and histopathologic examination of intestinal mucosa to determine mucosal thickness and structural damage. Serum bilirubin and alkaline phosphatase levels confirmed OJ in all animals with CBD transection. The mucosal damage score was significantly reduced in jaundiced animals receiving PGE1 compared to jaundiced controls (2.15 +/- 0.74 vs 5.3 +/- 0.59; p < .00001) and mucosal thickness was greater (607 +/- 59.1 microm vs. 393 +/- 40.3 microm; p < .00001). The incidence of BT to MLNs decreased from 90% to 30% (p < .02) when jaundiced rats received PGE1. PGE1 treatment reduced the detection rate of viable enteric bacteria in the blood from 60% to 10% (p < .057). We conclude that administration of PGE1 provides protection against OJ-induced atrophy and damage of intestinal mucosa, and thereby prevents translocation of enteric bacteria to underlying tissues.     

原位肝移植大鼠肠道微生态状况研究

目的 探讨肝移植术后大鼠肠道微生态的变化.方法 将雄性Brown-Norway(BN)大鼠40只随机分成肝移植组(BN→BN,n=16,共8对)、模拟移植组(n=8)、假手术组(n=8)和对照组(n=8),24 h后处死,分析肠道菌群构成、回肠末端超微结构变化、血浆内毒素水平以及细菌易位至肝、脾、肾和肠系膜淋巴结的比例.结果 肝移植术后24 h存在明显的肠道菌群紊乱,表现为肠杆菌科细菌和肠球菌数量增加(P<0.05),乳杆菌和双歧杆菌数量下降(P<0.05),移植组与模拟移植组存在肠黏膜上皮细胞微绒毛的损伤;肝移植组血浆内毒素水平升高(P<0.01),细菌易位至肝脏、脾脏和肠系膜淋巴结的阳性率增加(P值均<0.05);与模拟移植组比较,肝移植组细菌易位至肝脏的阳性率增加(P<0.05).结论 肝移植术后存在一定程度的肠道微生态紊乱和肠道屏障功能损伤,可能与肝移植手术过程中所经历的缺血再灌注过程有关.     

Role of bacterial adherence and the mucus barrier on bacterial translocation: effects of protein malnutrition and endotoxin in rats.

OBJECTIVE: The purpose of the study was to investigate the potential relations between mucosal bacterial adherence, intestinal mucus and mucin content, and bacterial translocation. SUMMARY BACKGROUND DATA: The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most bacterial infections that originate at mucosal surfaces, such as the gut. The intestinal mucus layer appears to function as a defensive barrier limiting micro-organisms present in the intestinal lumen from colonizing enterocytes. Consequently, studies focusing on the biology of bacterial adherence to the intestinal mucosa likely are to be important in clarifying the pathogenesis of gut origin sepsis. METHODS: To explore the relations between intestinal bacterial adherence, mucus bacterial binding, and bacterial translocation, two models were used. One (protein malnutrition) in which profound alterations in intestinal morphology occurs in the absence of significant translocation and one (endotoxin challenge) in which bacterial translocation occurs and intestinal morphology is relatively normal. RESULTS: Protein malnutrition was not associated with bacterial translocation and measurement of enteroadherent, mucosally associated bacterial population levels documented that the total number of gram-negative enteric bacilli adherent to the ileum and cecum was less in the protein-malnourished rats than in the normally nourished animals (p < 0.01). Furthermore, there was an inverse relation between the duration of protein malnutrition and bacterial adherence to the intestinal mucosa (r = 0.62, p < 0.002). In contrast, after endotoxin challenge, the level of enteroadherent bacteria was increased and bacterial translocation was observed. The binding of Escherichia coli to immobilized ileal mucus in vitro was decreased significantly in protein-malnourished rats, whereas E. coli binding to insoluble ileal mucus was increased in the rats receiving endotoxin. CONCLUSIONS: This study indicates that the adherence of bacteria to the intestinal mucosal surface is an important factor in bacterial translocation, that intestinal mucus modulates bacterial adherence, and that increased levels of mucosally associated bacteria are associated with a loss intestinal barrier function to bacteria.     

不同胆汁引流方式对梗阻性黄疸大鼠肠黏膜屏障功能的影响及机制

目的：探讨不同胆汁引流方式对梗阻性黄疸（OJ）大鼠肠黏膜功能的影响及其机制。 方法：将60只SD大鼠采用胆总管结扎法制作OJ模型,1周后随机均分为无引流组（不行胆汁引流术）,内引流组（行胆汁内引流术）和外引流组（行胆汁外引流术）,引流时间1周。以20只假手术大鼠为对照组,实验共2周,结束时分别用ELISA法和Western blot法检测各组血清内毒素水平和小肠黏膜组织闭锁蛋白（occludin）及闭锁小带蛋白1（ZO-1）的表达,并观察小肠黏膜组织形态学改变。 结果：大鼠造模后出现明显的OJ表现,二次手术后,内引流组大鼠一般情况明显好于无引流组和外引流组。无引流组和外引流组OJ大鼠血清内毒素水平明显升高,与对照组比较,差异均有统计学意义（均P<0.01）,而无引流组与外引流组间内毒素水平差异无统计学意义（P>0.05）;内引流组OJ大鼠血清内毒素水平较无引流组和外引流组明显下降（均P<0.01）,与对照组水平无统计学差异（P>0.05）。与对照组比较,无引流组和外引流组OJ大鼠小肠黏膜组织occludin及ZO-1蛋白表达均明显降低（均P<0.01）,且外引流组两者表达水平降低较无引流组更为明显（均P<0.01）;内引流组OJ大鼠的occludin及ZO-1的表达水平明显高于无引流组和外引流组（均P<0.01）,且基本接近对照组（均P>0.05）。病理学观察显示,无引流组和外引流组OJ大鼠肠黏膜结构破坏,大量或中量炎性细胞浸润,而内引流组OJ大鼠组肠黏膜结构完整,仅见少量炎性细胞浸润。 结论：胆汁内引流对OJ大鼠肠黏膜屏障具有保护作用,其机制可能与胆汁维持肠黏膜上皮细胞间紧密连接相关蛋白的表达有关。