Exendin-4对hIAPP转基因鼠胰岛功能的改善作用  

Improvement effect of Exendin-4 on islet function of hIAPP transgenic mice

作　　者：刘辰 邹庆宝 赵济全 LIU Chen;ZOU Qingbao;ZHAO Jiquan(Department of Doctor-Patient Relations,Section of Medical Administration,the Eighth Affiliated Hospital of Sun Yat-Sen University of Futian District in Shenzhen City,Guangdong,Shenzhen 518033,China)

机构地区：[1]中山大学附属第八医院(深圳福田)医务部医患关系科,广东深圳518033

出　　处：《中国医药科学》2022年第11期27-30,共4页China Medicine And Pharmacy

基　　金：广东省自然科学基金项目(2017A030313766)。

摘　　要：目的探究Exendin-4对hIAPP转基因鼠的保护作用及其可能的作用机制。方法正常小鼠和hIAPP转基因鼠分别注射PBS和Exdendin-4,共分为四组:正常小鼠对照组(WT+PBS)、正常小鼠注射Exendin-4组(WT+Ex-4)、hIAPP小鼠对照组(homo+PBS)、hIAPP小鼠注射Exendin-4组(homo+Ex-4),每组6只。对四组小鼠进行2个月每天一次的腹腔注射,给药结束后进行葡萄糖耐受实验;体外培养Min6胰岛β细胞,取对数生长期细胞分别加入2.5、5、10、20μM的hIAPP完全培养基,检测细胞周期相关蛋白的表达;分离小鼠原代胰岛细胞,Annexin V-FITC检测细胞凋亡;提取小鼠胰腺组织蛋白,检测周期相关蛋白表达水平变化。结果homo+PBS组小鼠葡萄糖耐受能力显著降低,差异有统计学意义(P<0.05),hIAPP体外处理Min6细胞会剂量依赖式下调ABC蛋白及周期相关蛋白CCND2和CCND3的蛋白表达。相反,homo+Ex-4组的小鼠葡萄糖耐受能力显著增强,差异有统计学意义(P<0.05),原代胰岛细胞的凋亡比例明显降低,细胞周期蛋白CCND2和CCND3的表达水平增加。结论Exendin-4对hIAPP转基因鼠造成的胰岛损伤具有保护作用,其机制与调控胰岛细胞增殖和凋亡有关。Objective To investigate the protective effect of Exendin-4 on transgenic mice of human islet amyloid polypeptide(hIAPP)and its possible mechanism.Methods Normal mice and hIAPP transgenic mice were injected with PBS and Exdendin-4 respectively.And they were divided into the control group of normal mice(WT+PBS,n=6),the Exendin-4 injection group of normal mice(WT+Ex-4,n=6),the control group of hIAPP mice(homo+PBS,n=6)and the Exendin-4 injection group of hIAPP mice(homo+Ex-4,n=6).Four groups of mice were injected intraperitoneally once a day for 2 months,and glucose tolerance test was carried out after administration.Min6 isletβcells were cultured in vitro,and 2.5,5,10 and 20μM hIAPP complete medium was added to logarithmic phase cells to detect the expression of cell cycle-related proteins.Primary mouse islet cells were isolated,and apoptosis was detected by Annexin V-FITC.Mouse pancreatic tissue protein was extracted,and the expression level of cycle related protein was detected.Results The glucose tolerance of mice in the homo+PBS group was significantly reduced,with statistically significant differences(P<0.05).The expression of ABC protein and cycle-related proteins CCND2 and CCND3 was down-regulated in a dose-dependent manner by hIAPP in vitro treatment of Min6 cells.On the contrary,the glucose tolerance of mice in the homo+Ex-4 group was significantly enhanced,with statistically significant differences(P<0.05).The proportion of apoptosis in primary islet cells was significantly reduced,and the expression levels of cell cycle proteins CCND2 and CCND3 were increased.Conclusion Exendin-4 has a protective effect on islet damage caused by hIAPP transgenic mice,and its mechanism is related to regulating the proliferation and apoptosis of islet cells.

关 键 词：EXENDIN-4 胰岛淀粉样多肽 细胞增殖 细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]