胆汁性肝硬化大鼠肾细胞凋亡及其机制  

Increased renal cell apoptosis and its mechanism in rats with biliary cirrhosis

作　　者：王利娜[1] 姜慧卿[1] 杨晶[2] 王玉珍[2] 吕晓萍[2] 

机构地区：[1]河北医科大学第二医院消化科 [2]河北省人民医院消化科,河北省石家庄市050051

出　　处：《世界华人消化杂志》2008年第24期2702-2707,共6页World Chinese Journal of Digestology

基　　金：河北省卫生厅科研基金资助课题;No.07009;河北省强势特色学科资助项目~~

摘　　要：目的:探讨胆汁性肝硬化大鼠肾脏病理组织学改变、肾脏细胞凋亡及其机制.方法:应用胆总管结扎(CBDL)技术制备大鼠胆汁性肝硬化模型.将SD大鼠随机分为:假手术组(SO)、CBDL2wk组与5wk组.显微镜下观察肝脏和肾脏组织学改变;生化法测定内生肌酐清除率(Ccr),比色法测定肾组织丙二醛(MDA)含量,TUNEL法检测肾组织细胞凋亡,免疫组化测定Bcl-2,Bax蛋白的表达.结果:CBDL大鼠2wk发生肝纤维化,5wk则形成肝硬化;5wk时肾小管上皮细胞有脱落、坏死;电镜下基底膜不规则增厚,系膜增宽,上皮细胞足突融合.模型大鼠5wk组Ccr明显降低,较2wk组与SO组有显著性差异(1.10±0.03vs1.40±0.03,1.80±0.02,P<0.05或0.01),肾组织丙二醛5wk组较2wk组与SO组显著性增高(4.07±0.51vs2.32±0.85,0.79±0.37,均P<0.01);模型大鼠5wk组肾组织凋亡指数显著性高于2wk组和SO组(68.36%±8.71%vs24.08%±2.59%,11.43%±2.77%;均P<0.01).SO组、2wk组及5wk组Bcl-2逐渐下降,Bax表达则逐渐升高,各组间有显著差异(P<0.05).结论:胆汁性肝硬化大鼠存在肾病理组织学改变与细胞凋亡;凋亡抑制蛋白Bcl-2低表达和凋亡诱导蛋白Bax高表达在肾损害中起作用.AIM： To investigate the renal pathological changes, cell apoptosis and expression of Bcl-2 and Bax proteins in rats with hepatic cirrhosis induced by common bile duct ligation （CBDL）. METHODS： Hepatic cirrhosis was induced by CBDL in SD rats. Thirty rats were randomized to 3 groups： sham operation group, 2-wk CBDL group and 5-wk CBDL. Hepatic and renal tissues were collected for pathohistological observation under microscope; the creatinine clearance rate （Ccr） and renal malonaldehyde （MDA） content were measured by biochemical method and spectrophotometric method, respectively; the apoptosis of renal cells was detected by TUNEL method; finally, the levels of Bcl-2 and Bax protein expression were examined by immunohistochemistry. RESULTS： Hepatic histological examination showed that hepatic fibrosis occurred in 2-wk CBDL group and biliary cirrhosis in 5-wk CBDL. In the 5-wk CBDL group, desquamation and necrosis of renal tubule epithelia were found by HE staining, and irregular thickening of glomerular basement membrane, mesangial expansion and fusion of epithelial foot processes were observed by electron microscopy. The Ccr significantly decreased （1.10 ± 0.03 vs 1.40 ± 0.03, 1.80 ± 0.02; P 〈 0.05 or 0.01） while MDA content increased （4.07 ± 0.51 vs 2.32 ± 0.85, 0.79 ± 0.37, both P 〈 0.01） in the 5-wk CBDL group in comparison with that in the 2-wk CBDL group or sham operation group. The apoptotic rate of renal cells was significantly higher in the 5-wk CBDL group than that in the 2-wk CBDL group or sham operation group （68.36% ± 8.71% vs 24.08% ± 2.59%, 11.43% ± 2.77%; both P 〈 0.01）. Bcl-2 protein decreased while Bax protein increased by turns in sham operation group, 2-wk CBDL group and 5-wk CBDL group （P 〈 0.05）. CONCLUSION： There are renal histopathological changes and cell apoptosis in rats with CBDL-induced hepatic cirrhosis, and low expression of Bcl-2 protein and high expression of Bax protein play important roles in the renal injury induced by CBDL ci

关 键 词：肝硬化 肾脏 细胞凋亡 Bcl-2 BAX 丙二醛 肌酐清除率 比色法 TUNEL法 免疫组化 

分 类 号：R575.2[医药卫生—消化系统]