外源性转化生长因子-β1对急性梗阻性胆管炎肝损伤的干预作用  

Effect of exogenous transforming growth factor-β1 on the liver injury in acute obstructive cholangitis

作　　者：高登辉[1] 王恒毅[1] 王景钧[1] 汪继东[1] 方征[1] 

机构地区：[1]安徽医科大学第一附属医院急诊外科,合肥230032

出　　处：《中华实验外科杂志》2014年第3期541-543,共3页Chinese Journal of Experimental Surgery

基　　金：安徽省教育厅自然科学基金资助项目（KJ2012Z200）

摘　　要：目的 观察外源性转化生长因子-β1（TGF-β1）对急性梗阻性胆管炎肝损伤的干预作用,探讨TGF-β1减轻肝损伤的分子机制.方法 健康Wistar大鼠90只,随机分为6组,实验组结扎胆总管并注入大肠杆菌建立大鼠急性梗阻性胆管炎模型,尾静脉直接注射外源性TGF-β1（10 mg/kg）进行干预,观察干预后24 h大鼠肝脏病理改变;并利用生化分析仪检测干预后0～48 h血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平评价外源性TGF-β1对肝损伤的干预作用;酶联免疫吸附试验（ELISA）及Western blot分别检测0～48 h血清及肝脏中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）的表达水平.结果 TGF-β1干预24h后,急性梗阻性胆管炎（AOC）/TGF-β1组ALT、AST分别为（99.0±11.4）、（92.6±11.8） IU/L;48 h后分别为（145.3 ±15.7）、（133.0±15.5） IU/L,均较AOC组下降,差异有统计学意义（P＜0.05）.TGF-β1干预24h后,AOC/TGF-β1组血清中TNF-α、IL-1β表达水平分别为（132.6±10.3）、（145.9±18.5） ng/L;48 h后分别为（243.6±15.7）、（279.2±20.3）ng/L,均较AOC组下降,差异有统计学意义（P＜0.05）.TGF-β1干预24h后Western blot检测AOC/TGF-β1组肝组织中TNF-α和IL-1β的蛋白表达量均较AOC组降低,差异有统计学意义（P＜0.05）.结论 通过外源性TGF-β1直接干预,可以减轻急性梗阻性胆管炎肝损害,改善肝功能,TGF-β1的这一作用可能是通过下调TNF-α、IL-1β在全身或肝脏中的蛋白表达水平来实现的.Objective To determine the effects of exogenous transforming growth factor （TGF）-β1 on the liver injury in acute obstructive cholangitis （AOC） and the mechanism.Methods After 90 Wistar rats were divided into 6 groups randomly,a rat model of AOC was established by ligating choledochus and injecting escherichia coli 25922 into the ligated choledochus.After treatment of exogenous TGF-β1 （10 mg/kg） for 0-48 h,the expression levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β protein in the liver tissue were assayed by using Western blotting,and the levels of serum TNF-α and IL-1β were determined by using enzyme linked immunosorbent assay （ELISA）.The pathological changes of liver injury were observed under the microscopy using hematoxylin and eosin （HE） staining,and alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined at 0-48 h.Results Compared to the control groups,histopathological liver injury was alleviated.After the treatment with TGF-β1 for 24-48 h,the levels of ALT and AST were （99.0 ± 11.4） and （92.6 ± 11.8） IU/L at 24 h,and those were （145.3 ± 15.7） and （133.0 ± 15.5） IU/L at 48 h respectively,where were markedly reduced as compared with AOC group （P ＜0.05）.After treatment with TGF-β1 for 24-48 h,the serum TNF-α and IL-1β protein levels were （132.6 ± 10.3） and （145.9 ± 18.5） ng/L at 24 h,and （243.6 ± 15.7） and （279.2 ±20.3） ng/L at 48 h respectively,which were obviously decreased,as compared with AOC group （P ＜ 0.05）.Moreover the TNF-cα and IL-β1 protein levels in the liver tissues were also decreased in AOC/TGF-β1 groups （P ＜0.05）.Conclusion Exogenous TGF-β1 can alleviate the liver injury in acute obstructive cholangitis,which may be related with the reduced TNF-α and IL-1β protein levels.

关 键 词：转化生长因子-Β1 急性梗阻性胆管炎 肝损伤 肿瘤坏死因子-α 白细胞介素-1Β 

分 类 号：R285.5[医药卫生—中药学]