ECM、MMP-1及TIMP在酒精性肝病伴发肠黏膜损伤中的作用

摘要

Objective To study the effect of extracellular matrix (ECM) , matrix metalloproteinases-1 ( MMP-1) and tissue inhibitor of metalloproteinase (TIMP) on intestinal mucous injury in mice with alcohol-induced liver disease. Methods Twenty c57/BL mice were randomly divided into control group and model group (10 in each). The control group mice were fed with Lieber Decarli liquid without ethanol, and mice in the model group were fed with 4% ethanol Lieber De-carli liquid. The serum endotoxin was examined after 10 weeks, intestinal and liver tissues were assessed with HE staining. The intestinal mucosa of collagen fibers was observed by masson staining. The expression of ECM in intestine was detected by immunofluorescence method, and the expression of MMP-1 , TIMP in intestine were detected by immunohistochemical method. Results The serum endotoxin in the model group was much higher than that in control group (P<0. 01). The histopathological score of colon injury in the model group was much higher than that in control group (P < 0. 01) . The mucosa collagen fiber in the modle group was thickened than that in control group. The expression of ECM in the model group was much higher than that in control group. The expression of MMP-1 , TIMP were no obvious change in the model group and control group. Conclusion Alcoholic liver disease complicates with intestinal mucosa collagen deposition and a lot of ECM expression.%目的 探讨细胞外基质(ECM)、金属基质蛋白酶-1(MMP-1)、组织金属蛋白酶抑制物(TIMP)在酒精性肝病伴发肠黏膜损伤中的作用.方法 将20只c57/BL小鼠随机分为对照组、模型组,每组10只.对照组饲喂Lieber-Decarli无酒精液体饲料,模型组饲喂含4％乙醇Lieber-Decarli液体饲料建立酒精性肝病模型,10周后处死小鼠,心脏采血检测血清内毒素；分别取肝组织、肠组织进行形态学检查,masson染色观察肠黏膜胶原纤维；免疫荧光定位ECM表达；免疫组织化学法检测MMP-1、TIMP-1表达.结果 模型组血清内毒素较对照组明显升高(P＜0.01)；模型组结肠损伤病理学评分较对照组明显升高(P＜0.01)；模型组肠黏膜胶原纤维较对照组明显增厚；模型组肠黏膜ECM表达明显高于对照组；模型组MMP-1、TIMP-1表达较对照组无明显改变.结论 酒精性肝病伴发肠黏膜胶原纤维的沉积及ECM的大量表达.