STAT3活化在脂多糖刺激大鼠胆管上皮细胞增殖中的作用  

Function of STAT3 activation in the proliferation of rat biliary epithelial cells induced by lipopolysaccharide

作　　者：陈莉萍[1] 郭毅斌[2] 戴睿武[3] 李昆[1] 王曙光[1] 董家鸿[1] 

机构地区：[1]第三军医大学西南医院全军肝胆外科研究所,重庆400038 [2]解放军第175医院烧伤科,福建福州363000 [3]成都军区总医院全军普通外科中心,四川成都610083

出　　处：《中国病理生理杂志》2007年第5期921-925,共5页Chinese Journal of Pathophysiology

基　　金：全军"十五"科研基金重点课题资助项目(No.2000322028);全军医学卫生科研基金科技攻关资助项目(No.06G071)

摘　　要：目的:探讨脂多糖(LPS)刺激大鼠肝内胆管上皮细胞(BEC)增殖过程中信号转导和转录激活因子3(STAT3)活化的意义。方法:大鼠随机分为对照组(control)、LPS组和雷帕霉素(RPM)处理组。分别于注射LPS后6、12、24、48和72h采用动态比浊法鲎试验测定血浆LPS水平,酶联免疫吸附试验(ELISA)法检测肝组织匀浆IL-6水平,激光扫描共聚焦显微镜(LSM)检测BEC内磷酸化STAT3(p-STAT3)水平,免疫组织化学法检测BEC增殖。结果:大鼠注射LPS后6h血浆LPS水平最高[(318±115)EU/L],48h接近control组水平[(29±11)EU/L];IL-6水平于注射LPS后12h达峰值[(653.4±168.8)ng/g蛋白],72h接近control组水平[(249.4±50.7)ng/g蛋白],LPS组BEC内p-STAT3的表达与IL-6水平呈显著正相关(r=0.944,P<0.05);BEC增殖指数在12h明显增加[(5.2±0.5)%],24h达到峰值[(12.8±3.0)%],72h接近control组水平[(4.2%±0.6%)];给予RPM明显减轻LPS诱导的细胞STAT3活化和BEC增殖。结论:LPS刺激导致肝组织IL-6分泌增加,后者可能通过STAT3介导BEC增殖。AIM： To investigate the significance of signal transducers and activation of transcription 3 （STAT3） in proliferation of rat intrahepatic biliary epithelial cell （BEC） induced by LPS. METHODS： Male Wistar rats were randomly divided into three groups ： normal control, endotoxemia （LPS） group and rapamycin （RPM） group. Plasma LPS was detected by kinetic turbidimetric limulus test at 6 h, 12 h, 24 h, 48 h, and 72 h after injury. IL -6 secretion in liver homogenate was determined by ELISA. P - STAT3 expression in BEC was analyzed by laser scan confocal microscopy. Proliferation of BEC was detected by immunohistochemistry. RESULTS： Plasm LPS level was maximum at 6 h [ （318 ± 115） EU/L] after injury and descended closely to control level at 48 h [ （29 ± 11 ） EU/L]. IL -6 expression peaked at 12 h （653.4 ng/g ± 168.8 ng/g protein） and closed to control level at 72 h （0. 013 ng/g ±0. 006 ng/g protein）. In LPS group, significant direct correlation between p- STAT3 expression in BEC and IL- 6 level in liver homogenate was found. BEC proliferation was induced by LPS at 12 h （5.2 ±0. 5） and reached the maximum level at 24 h, which was higher than the control level even at 72 h, while RPM abrogated STAT3 activation and BEC proliferation induced by LPS. CONCLUSION： LPS induces liver IL- 6 expression, which might activate BEC proliferation through STAT3 pathway.

关 键 词：脂多糖类 胆管 上皮细胞 白细胞介素6 信号转导 

分 类 号：R363[医药卫生—病理学]