胆汁淤积性肝纤维化大鼠肝组织中PTEN表达与肝星状细胞凋亡的关系研究  

Relationship of PTEN expression with apoptosis of hepatic stellate cells in liver tissues of rats with hepatic fibrosis induced by bile stagnation

作　　者：郝礼森[1,2] 张晓岚[1] 周智宏[2] 李玉林[2] 麻继臣[1] 安君艳[1] 姚冬梅[1] 房澍名[1] 姜慧卿[1] 

机构地区：[1]河北医科大学第二医院消化内科,河北省消化病重点实验室,河北省消化病研究所,石家庄050000 [2]华北煤炭医学院附属医院消化内科,河北唐山063000

出　　处：《解放军医学杂志》2010年第7期836-838,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(30872513)

摘　　要：目的探讨胆汁淤积性肝纤维化大鼠肝组织中磷酸酶张力蛋白同源物基因(PTEN)的动态表达与在体肝星状细胞(HSC)凋亡的关系。方法健康雄性SD大鼠50只,随机分为模型组(n=40)及假手术组(n=10)。模型组采用胆总管结扎法建立胆汁淤积性大鼠肝纤维化模型,并分别于结扎后1、2、3、4周(每个时间点取10只)麻醉后留取肝组织。假手术组大鼠亦于相应时间麻醉后留取肝组织。采用免疫组化法测定大鼠肝组织中PTEN蛋白的表达;采用末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末端标记法(TUNEL)及α-SMA免疫组化双染法检测在体活化HSC的凋亡情况。结果正常大鼠肝组织未见凋亡的HSC。随着肝纤维化程度加重,肝组织中PTEN蛋白的表达量逐渐减少(P<0.01),而活化HSC增多,凋亡HSC也增多。造模1、2、3、4周,大鼠肝组织的HSC凋亡指数(分别为4.57%±0.41%、4.02%±0.48%、3.45%±0.37%、2.88%±0.50%)逐渐减少(P<0.01)。大鼠肝纤维化组织中PTEN的蛋白表达量与在体HSC的凋亡呈显著正相关(r=0.76,P<0.01)。结论胆汁淤积性大鼠肝纤维化组织中PTEN的蛋白表达下调与在体活化HSC的凋亡减少相一致。Objective To explore the relationship of phosphatase and tensin homology （PTEN） deleted on chromosome ten with the apoptosis of hepatic stellate cells （HSCs） in liver tissues of rats with hepatic fibrosis induced by bile stagnation.Methods Fifty adult male SD rats were randomly divided into model group （n=40） and sham operation group （n=10）.The model of hepatic fibrosis was reproduced in model group by common bile duct ligation （BDL）.Liver tissue of rats in model group （1,2,3 and 4 weeks after BDL） and sham operation group were obtained.PTEN expression in liver tissue was detected by immunohistochemistry.Apoptosis of HSC was determined by dual staining of terminal deoxynucleotidy transferase UTP-nick end labeling （TUNEL） and α-SMA immunohistochemistry.Results Only a few apoptotic HSCs were found in normal livers.With the development of liver fibrosis,the expression of PTEN decreased gradually （P〈0.01）,while the number of activated and apoptotic HSCs increased.The apoptosis index of activated HSCs （4.57%±0.41%,4.02%±0.48%,3.45%±0.37% and 2.88%±0.50%,respectively,at 1,2,3 and 4 weeks after BDL） decreased gradually with the aggravation of liver fibrosis （P〈0.01）.The expression of PTEN had a significant positive correlation with the apoptosis index of activated HSCs in liver tissues of rats with induced hepatic fibrosis （r=0.76,P〈0.01）.Conclusion Down-regulation of PTEN expression is in accordance with the decrease of apoptotic activated HSCs in vivo in liver tissues of rats with hepatic fibrosis induced by biliary stagnation.

关 键 词：基因 pten 肝硬化 胆汁淤积 肝内 细胞凋亡 

分 类 号：R575.22[医药卫生—消化系统]