PI3K/AKT/Survivin通路在大鼠腹膜纤维化中的作用机制  

The role of PI3K/Akt/Survivin pathway in rat peritoneal fibrosis

作　　者：王乙安 陈静 赵恒 陆琪 凡碟 王莹[1] 晏玥 朱珠 陈芳[1] 皮成仙 者星炜[1] WANG Yi-an;CHEN Jing;ZHAO Hen;LU Qi;FAN Die;WANG Ying;YAN Yue;ZHU Zhu;CHEN Fan;PI Cheng-xian;ZHE Xing-wei(The Frst Affiliated Hospital of Kunming Medical University,Kunming650000,Yunnan,China)

机构地区：[1]昆明医科大学第一附属医院肾脏内科,云南昆明650000 [2]昆明医科大学基础医学院,云南昆明650500

出　　处：《广东医学》2018年第21期3165-3169,共5页Guangdong Medical Journal

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金(编号:2017FE467)

摘　　要：目的探讨磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/生存素(Survivin)信号通路在腹膜间皮细胞上皮-间充质转分化(EMT)中的作用。方法 20只雄性SD大鼠随机分为模型组和对照组,模型组每天给予42. 5 g/L葡萄糖腹膜透析液(100 m L/kg)腹腔注射建立大鼠腹膜间皮细胞EMT模型,对照组在相同条件下予等量的生理盐水腹腔注射。两组大鼠于4周末次腹膜透析后,留取腹膜组织,采用HE和Masson染色,观察腹膜组织形态学变化并测量腹膜组织厚度,采用实时定量PCR、Western印迹和免疫组化等方法检测腹膜组织p-AKT、AKT、Survivin的表达及EMT相关蛋白和mRNA的表达[紧密连接蛋白(ZO-1)、神经-钙黏素(N-cadherin)]。结果成功建立大鼠腹膜间皮细胞EMT模型,与对照组相比,模型组小鼠腹膜组织明显增厚,上皮细胞标志物ZO-1 mRNA及蛋白表达降低,间充质细胞标志物N-cadherin mRNA及蛋白表达升高,p-AKT、Survivin蛋白也明显升高(P <0. 05),AKT蛋白表达无明显变化(P> 0. 05)。结论 PI3K/AKT/Survivin信号通路参与腹膜间皮细胞EMT的发生与发展。Objective To investigate the role of PI3 K/Akt/Survivin signaling pathway in the peritoneal mesothelial cells epithelial-mesenchymal transition( EMT). Methods Twenty males SD rats were randomly divided into experimental group and control group. The peritoneal mesothelial cell EMT model was established in experimental group by given with daily intraperitoneal injection of peritoneal dialysis liquor( 4. 25% glucose,100 m L/kg),while the control group was given with placebo saline. Four weeks after peritoneal dialysis,the peritoneal tissue samples in the 2 groups were collected for pathological observation using HE and Masson staining. The quantitative real-time PCR,Western blotting and immunohistochemistry method were applied for assessment of p-Akt,Akt and Survivin in peritoneal tissues and the expression of ZO-1 and N-cadherin. Results The rat peritoneal mesothelial cell EMT model was successfully established,and compared with the control group,the peritoneal tissue in experiment group was significantly thickened,with significant down-regulation of ZO-1 mRNA and protein and up-regulation of mesenchymal cell marker N-cadherin,p-Akt and Survivin( P < 0. 05). Conclusion PI3 K/Akt/Survivin signaling pathway is involved in the occurrence and development of EMT in peritoneal mesothelial cells.

关 键 词：腹膜透析 上皮-间充质转分化 磷脂酰肌醇3-激酶 蛋白激酶B 生存素 

分 类 号：R572.2[医药卫生—消化系统]