选择性肠道去污染对肝硬化自发性细菌性腹膜炎肠黏膜通透性的影响

目的观察肝硬化自发性细菌性腹膜炎（SBP）肠黏膜通透性和形态结构的变化及选择性肠道去污染对其通透性的影响。方法按诊断标准,将28例肝硬化SBP患者随机分为治疗组（15例）和对照组（13例）,在肝硬化腹水常规治疗和全身应用抗生素抗感染的基础上,治疗组加用诺氟沙星口服选择性肠道去污染（SDD）。采用酶联免疫吸附法（ELISA）测定治疗前后二胺氧化酶（DAO）、D-乳酸（D-Lac）和内毒素（ET）的水平;HE常规染色观察肠黏膜形态结构的变化。结果 常规治疗可降低DAO、D-Lac和ET水平（P〈0.05）,加用SDD可进一步减轻肠黏膜损伤,降低肠黏膜通透性,防止细菌移位。结论 SDD对肝硬化SBP肠黏膜屏障具有保护作用。     

肝硬化的胃肠道并发症

肝硬化是慢性肝病的终末阶段,可影响到全身多器官功能。而肝硬化所致消化道损害临床上更为常见。肝硬化会导致胃肠动力下降、影响营养物质的消化吸收及破坏肠黏膜屏障功能,还会并发一系列胃肠道并发症,影响患者预后。临床上,更应重视肝硬化相关胃肠道并发症,做到早期监测、早期诊断和早期治疗,控制肝硬化病情进展、减少晚期并发症、提升患者生活质量。     

肝硬化患者肠黏膜通透性与Child—Pugh分级的相关性研究

目的探讨肝硬化患者肠黏膜通透性（IP）与Child—Pugh分级的相关性及肠道去污剂对肝硬化患者肠道屏障功能及肝功能状态的影响。方法按Child—Pugh分级标准将76例肝硬化患者分为A、B、C3组,并选择30例体检者作为对照组,采用高压液相色谱法检测各组患者尿液乳果糖／甘露醇排出比（L／M）;给予76例肝硬化患者选择性肠道去污剂,比较用药前后各组患者肝功能Child—Pugh分级和肠黏膜通透性。结果肝硬化患者尿乳果N／甘露醇排出比明显高于对照组（0．208±0．025vs0．057±0．019）,肝硬化患者按Child。Pugh分级各组尿乳果糖／甘露醇排出比也均明显高于对照组,差异有显著性（P〈0．01）;采用Spearman等级相关分析发现,肝功能Child—Pu巾评分与乳果糖／甘露醇排出比呈正相关（r=0．658,P〈0．05）;给予肠道去污药物2周后肝硬化Child-Pugh分级各组患者尿液乳果糖／甘露醇排出比与治疗前比较均明显下降（P〈0．05）,各组Child—Pugh评分均有改善。结论肝硬化患者的肠黏膜通透性与肝功能Child—Pugh评分呈正相关,即肠道通透性随肝功能下降而升高,肠黏膜通透性对于肝硬化患者的诊断和治疗有临床意义。     

肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎的影响

目的探讨肠黏膜通透性改变对肝硬化自发性细菌性腹膜炎（SBP）的影响。方法 采用高压液相色谱-示差法，检测45例住院肝硬化腹水患者（34例白发性腹膜炎和11例肝硬化无菌性腹水）治疗前后口服糖分子探针乳果糖、甘露醇后尿液排泄率比值（LAC／MAN）情况，评估病人肠黏膜通透性水平；采用鲎试剂三肽显色基质偶氮法检测病人治疗前后血浆内毒素（LPS）水平，另11例健康志愿者作为对照组结果治疗前肝硬化SBP尿LAC／MAN、血浆内毒素水平均显著高于无菌性腹水（SA）组和健康对照组（P均〈0．001）Pearson相关性分析：肝硬化腹水患者尿LAC／MAN改变与血浆LPS水平呈正相关（r=0．187，P〈0．001）治疗1周后肝硬化SBP患者尿LAC／MAN及血浆LPS水平平行下降。结论肝硬化SBP患者存在肠黏膜通透性异常，且肠黏膜通透性改变与内毒素血症有关．     

肝硬化腹水与肠黏膜屏障功能关系研究进展

腹水是失代偿期肝硬化常见的并发症之一。腹水出现后病死率显著增高。腹水产生的机制较为复杂,往往是多种因素共同导致的。近年来随着高通量测序技术及临床检测技术的发展,肝硬化患者肠道菌群及炎症反应的研究逐渐深入,其改变均会导致肠黏膜通透性增高,增加自发性细菌性腹膜炎的发病率,导致肝硬化腹水的发生发展。本文对肝硬化腹水与肠黏膜屏障功能的关系以及肝硬化腹水常规治疗对肠道菌群及炎症因子的影响进行综述,以期为进一步探索肝硬化腹水的发病机制及治疗提供思路。     

梗阻性黄疸对肠黏膜屏障的影响

肠黏膜屏障包括机械屏障、免疫屏障、生物屏障和化学屏障,四者共同维持肠黏膜的正常防御功能。梗阻性黄疸患者引起肠黏膜屏障损伤,导致细菌移位及内毒素血症,后者又加重屏障功能障碍。本文主要就梗阻性黄疸对肠黏膜屏障损伤的机制作一综述。     

慢性腹泻肠黏膜结构和屏障功能的变化

目的 探讨慢性腹泻患者肠黏膜结构和屏障功能的变化.方法 对33例慢性腹泻患者和30名健康志愿者行结肠镜检查,并在镜下取回肠末端和回盲部黏膜各3块,光镜下观察肠黏膜的组织结构,同时测定血浆内毒素水平,以评价肠黏膜屏障功能.结果 慢性腹泻患者光镜下可见回肠末端有绒毛顶端上皮细胞水肿、脱落,但与健康志愿者无明显差异(P>0.05);回盲部可见被覆上皮细胞明显水肿、脱落和破溃,甚至被覆上皮细胞完全脱落,与健康志愿者有明显差异(P<0.05).慢性腹泻患者和健康志愿者血中内毒素含量无统计学差异(P>0.05).结论 慢性腹泻患者可能存在结肠黏膜屏障损害.     

重症急性胰腺炎中肠道免疫功能紊乱的研究进展

重症急性胰腺炎患者常伴有肠黏膜透性增高,肠黏膜免疫功能异常, 出现肠道菌群、内毒素移位, 引起继发感染, 诱发多脏器功能不全, 死亡率极高. 因此, 肠黏膜通透性增高及免疫功能异常与重症急性胰腺炎病程后期继发感染密切相关. 但肠黏膜免疫功能异常的确切机制尚不明确, 有待于进一步研究.     

肝硬化患者肠黏膜屏障功能变化及谷氨酰胺干预价值的研究

目前已有研究证实肠黏膜屏障功能障碍在肝硬化疾病的发生、发展中起着重要作用,针对其发生机制及相关临床干预等的研究亦越来越受到学者的重视。在相关临床干预措施中,谷氨酰胺维护肠黏膜屏障的作用得到广泛认同。通过查阅国内外相关文献资料,本文将就此方面的研究加以概述。     

炎症性肠病肠黏膜屏障损伤机制

肠黏膜屏障是指将肠腔内细菌、抗原等物质与肠黏膜固有层免疫细胞隔离开,避免固有层免疫细胞激活的肠黏膜结构,要由肠黏膜基底膜、上皮细胞层及其表面的黏液层所构成.炎症性肠病(innammatory bowel diseasc,IBD)肠黏膜屏障损伤的机制为:IBD发病时,肠黏膜所产生的大量炎症细胞因子、炎症介质等损伤肠上皮细胞,诱导上皮细胞凋亡;影响上皮细胞紧密连接蛋白的表达及分布,破坏上皮细胞间紧密连接;抑制黏蛋白的产生,破坏上皮细胞表面的黏液层,造成肠黏膜屏障障碍.     

暴发性肝衰竭小鼠细菌侵袭肠黏膜方式的研究

目的 通过研究细菌侵袭肠黏膜屏障的方式,探讨暴发性肝衰竭(FHF)并发自发性腹膜炎(SBP)的机制.方法 取240只雄性BALB/c小鼠,分为等渗盐水(NS)组(40只)、脂多糖(LPS)组(40只)、氨基半乳糖(GalN)组(40只).FHF模型组(120只).分别腹腔注射相同体积的NS、LPS(10μg/kg)、GalN(800 mg/kg)、LPS(10μg/kg)/GalN(800 mg/kg).注射处理后,分别于2、6、9、12 h和24 h处死小鼠(每个时间点处死8只小鼠).实验小鼠均在相应时间点摘取眼球,留取血清,并断头处死动物,留肝脏及大肠组织标本.用全自动生物化学分析仪检测ALT;对肝组织和大肠组织进行HE染色检测;透射电镜观察大肠黏膜超微结构及细菌侵袭肠黏膜的方式.用SPSS13.0统计软件进行数据分析,两组间ALT水平的分析采用Mann-Whitney U检验.结果 FHF模型组ALT水平、肝组织病理学检测结果及病死率和临床表现均符合FHF的诊断标准.4组小鼠注射处理后9 h,HE染色发现大肠组织仅有轻微水肿及少量炎性细胞浸润,此时,透射电镜下观察发现FHF模型组肠上皮细胞微绒毛断裂、脱落、变短,紧密连接(TJs)不完整,细胞器变化明显,HE染色发现FHF模型组肝脏呈成片的出血性坏死,残存的肝细胞肿胀,出血坏死区见较多炎性细胞浸润,但NS组、LPS组、GalN组肝脏组织病理形态及大肠黏膜超微结构变化不明显.FHF模型组注射处理后6～9 h,细菌以胞饮的形式穿入肠壁,细菌穿入肠壁区域的肠道黏膜绒毛脱落,TJs出现断裂,注射处理后12 h发现穿入的细菌以囊胞的形式存在.结论 LPS(10μg/kg)/GalN(800 mg/kg)联合注射建立的FHF小鼠模型是成功的.FHF时,肠黏膜TJs的断裂可能为肠道内细菌进入肠黏膜提供了条件,TJs的断裂可能是FHF并发SBP的原因之一.

Abstract：

Objective To explore the mechanism of fulminate hepatic failure (FHF) complicated with spontaneous peritonitis (SBP) through the research of bacteria invading the intestinal mucosa barrier.Methods 240 BalB/c male mice were divided into four groups as isotonic NS group (n = 40), lipopolysaccharide (LPS) group (n = 40), galactosamine (GalN) group (n = 40) and FHF model group (n = 120). Each mouse received same volume of NS, LPS (10 μ g/kg), GalN (800 mg/kg) or LPS (10 μ g/kg)/GalN (800 mg/kg)intraperitoneal injection according to its group. 8 mice were executed at 2, 6, 9, 12 and 24 hours after injection, respectively, and the liver and intestinal tissue samples were taken at the same time. ALT was measured by automatic biochemical analyzer and was compared between groups using Mann-Whitney U test.Liver and intestinal tissue received HE staining. The ultrastructure of intestinal mucosa and the method by which bacteria invaded the intestinal mucosa were observed by transmission electron microscopy. All data were analyzed by SPSS13.0 statistic software. Results ALT level, results of hepatic pathology, mortality and clinical manifestations of mice in the FHF model group met the diagnostic criteria of FHF. Intestinal tissue was found with slight edema and little inflammatory cells infiltration through HE staining in all the 4 groups of mice 9 hours after injection. Microvilli were found broken, shed and shorten in the intestinal epithelial cells with incomplete tight junction (TJs) and obviously changed organelles in the FHF model group of mice observed by transmission electron microscope. Mass hemorrhagic necrosis of liver cells with remnant liver cells swelling and many inflammatory cells infiltration by HE staining in the FHF model group. But the changes in hepatic pathology and intestinal mucosa ultrastructure were not so obvious in the mice of NS, LPS and GalN groups. Bacteria penetrated the intestinal wall by pinocytosis 6-9 hours after injection in the FHF model group, the microvilli were broken off and TJs turned rupture in the areas that the bacteria penetrated.The bacteria were found in the form of cyst 12 hours after injection. Conclusions LPS (10 mg/kg)/GalN (800 mg/kg) combined injection was successful in establishing the FHF mice model. The rupture of TJs may provide conditions for intestinal bacteria to penetrate the intestinal mucosa in FHF. Rupture of TJs may be one of the reasons why FHF was complicated with SBP.     

Dynamic changes and mechanism of intestinal endotoxemia in partially hepatectomized rats

AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into three groups： normal control （NC） group, partially hepatectomized （PH） group and a sham-operated （SO） group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation （ 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h）. NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin （ET） and diamine oxidase （DAO） levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells （KCs） in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS： Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation （r = 0.757, P 〈 0.05） between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum （La） particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION： The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of     

肝硬化后肠道细菌移位的发生与防治进展

肝硬化后易并发内毒素血症、细菌及真菌感染,肠道细菌移位是其并发感染,甚至多脏器功能衰竭的主要原因之一。有关动物实验研究及临床观察发现,肠粘膜屏障功能受损、机体免疫功能下降是发生肠道细菌移位的主要机制。预防和纠正肠道菌群紊乱、加强肠道营养支持、增强机体免疫功能等能有效防治肠道细菌移位。     

Decreased IgA+ plasma cells and IgA expression in acute liver necrosis mice

AIM: To investigate the number of intestinal immunoglobulin A (IgA+) plasma cells and expression of intestinal IgA in mice with acute liver necrosis. METHODS: A model of acute liver necrosis was established by intraperitoneal injection of galactosamine (GalN) and lipopolysaccharide (LPS). Sixty mice were randomly divided into one of 4 equal groups: normal control, acute liver necrosis, LPS, or GalN. Hematoxylin and eosin staining, immunohistochemistry, and an enzyme-linked immunosorbent assay were employed to assess liver and intestinal injury, count intestinal IgA+ plasma cells, and measure the expression level of IgA and interferon γ (IFN-γ) in the small intestinal mucosa of mice. RESULTS: Injured intestinal mucosa was observed in the acute liver necrosis group but not in the normal, LPS or GalN groups. Compared with the normal group,intestinal IgA+ plasma cells were slightly decreased in the LPS and GalN groups [429 ± 20 per high power f ield (HPF), 406 ± 18/HPF, respectively], whereas they were markedly decreased in the acute liver necrosis group (282 ± 17/HPF vs 495 ± 26/HPF in normal group, P < 0.05). The expression of intestinal IgA was also slightly decreased in LPS and GalN groups, but was markedly reduced in the acute liver necrosis group as determined by enzyme-linked immunosorbent assay (P < 0.05). In contrast, the level of IFN-γ was slightly increased in LPS, GalN and acute liver necrosis groups, but with no statistical signif icance (P > 0.05). CONCLUSION: Intestinal IgA+ plasma cells and IgA expression levels indicating that mucosal immune barrier dysfunction, does exist in acute liver necrosis.     

模拟高原低氧环境暴露下家兔小肠黏膜扫描电镜观察

目的探讨高原低氧环境暴露对肠黏膜的损伤作用及对急性高原病发生发展的影响。方法将健康家兔暴露于海拔5000m的模拟高原低氧环境下3天,取小肠黏膜标本扫描电镜观察。结果高原环境暴露下家兔小肠黏膜表面粗糙不平,绒毛卷曲倒伏凝结呈板块状,表面可见较多的缺损,缺损处可见大量纤维细丝及漏出的双凹碟形红细胞。结论高原低氧暴露能引起严重的肠黏膜结构破坏,使黏膜屏障功能减弱,     

Protective effect of rhubarb on the intestinal mucosal barrier

AIM: To investigate the mechanism of rhubarb protection of the gut barrier.METHODS: The gut barrier damage models caused by hemorrhagic shock and intraperitoneal endotoxin were used to study the protective effect of rhubarb on the intestinal mucosal barrier. Rats were randomly divided into four groups, as follows: treatment (rhubarb) group; Positive control group; Negative control group; Placebo treatment group. Plasma endotoxin, tissue superoxidedismutase (SOD) and lipoperoxide (LPO) concentrations were measured and histological analysis was performed. Rhubarb was observed to have a protective effect on the gut.RESULTS: Rhubarb decreased intestinal permeability, attenuated endotoxin absorption (endotoxin serum levels: shock group 0.557 EU/mL ± 0.069 EU/mL vs rhubarb group 0.345 EU/mL ± 0.055 EU/mL), and decreased tissue SOD and tissue LPO levels (SOD serum, intestine and liver levels: endotoxin group 122.92 NU/mL ± 43.19 NU/mL, 292.24 NU/mL ± 88.76 NU/mL, 272.70 NU/mL ± 85.79 NU/mL vs rhubarb group 312.23 NU/mL ± 54.93 NU/mL, 391.09 NU/mg ± 98.16 NU/mg, 542.86 NU/mg ± 119.93 NU/mg; LPO content in the intestine and liver: endotoxin group 8.57 μmol/L ± 2.58 μmol/L, 86.97 μmol/L ± 46.54 μmol/L vs rhubarb group 3.05 μmol/L ± 1.13 μmol/L, 13.18 μmol/L ± 19.64 μmol/L). Gut histopathology revealed that rhubarb promoted goblet cell proliferation, increased mucus secretion and protected intestinal mucosa in the hemorrhagic shock model.CONCLUSION: Rhubarb may protect the gut barrier by decreasing intestinal permeability, scavenging oxygen free radicals, and promoting goblet cell proliferation within the intestinal mucosa.     

Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats

AIM： To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis （NASH） in rats. METHODS： Thirty-two Sprague-Dawley （SD） rats were randomly divided into control group and model group. Rats in the control group were given normal diet, and rats in the model group were given fat-rich diet. Eight rats in each group were killed at end of the 8th and 12th wk, respectively. The levels of endotoxin, D-xylose, TG, TC, ALT and AST, intestinal tissue SOD and MDA as well as intestinal mucus secretory IgA （sIgA） were measured. The pathology of liver was observed by HE staining. RESULTS： At end of the 8th wk, there was no marked difference in the levels of endotoxin, D-xylose and sIgA between the two groups. At end of the 12th wk, rats in the model group developed steatohepatitis and had a higher serum level of endotoxin （P = 0.01） and D-xylose （P = 0.00） and a lower serum level of sIgA （P = 0.007）. CONCLUSION： Intestinal mucosa barrier malfunction may exist in NASH rats and may be an important promoter of NASH in rats.     

早期细胞凋亡在创伤性脑损伤肠黏膜屏障应激性变化中的作用

目的 探讨早期细胞凋亡在创伤性脑损伤(TBI)大鼠肠黏膜屏障应激性变化中的作用.方法 选用雄性Wistar大鼠64只,随机分为TBI组(32只)和假手术对照组(32只).2组大鼠分别按术后6、12、24和48 h时相点分为4个亚组(每个亚组8只).在光镜和透射电镜下观察肠黏膜组织形态学变化,同时用Annexin Ⅴ-PI双染法经流式细胞仪检测各组早期细胞凋亡率.结果 光镜下TBI组可见肠黏膜上皮细胞受损,电镜下可见其细胞间紧密连接较假手术对照组增宽,并可见典型的凋亡细胞.TBI组的创伤后早期即可见肠黏膜细胞的凋亡率较假手术对照组明显升高[6 h:(13.5±3.7)%比(6.1±1.7)%,P＜0.05;12 h:(66.1±6.0)%比(5.2±1.1)%,P＜0.05;24 h:(39.8±4.8)%比(8.4±2.6)%,P＜0.05;48 h:(7.5±1.3)%比(6.6±0.5)%].结论 大鼠TBI后的早期,肠黏膜屏障功能即可受损,肠黏膜上皮细胞早期凋亡率的增加可能在这一病理生理过程中起着重要作用.