胰岛素样生长因子1抑制高糖诱导大鼠胃平滑肌细胞内质网应激及其机制的研究  

IGF-1 inhibits endoplasmic reticulum stress in rat gastric smooth muscle cells induced by high glucose and its potential mechanism

作　　者：杨昆鑫 方学森 金政 张默函 YANG Kunxin;FANG Xuesen;JIN Zheng(Department of Histology&Embryology,Yanbian University College of Medicine,Yanji 133000,China)

机构地区：[1]延边大学医学院组织学与胚胎学教研室,延吉133000

出　　处：《中国糖尿病杂志》2020年第4期286-291,共6页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81560142);吉林省教育厅“十三五”科学技术项目(JJKH20191115KJ);延边大学大学生创新创业训练资助项目(YDCXCY2019022)。

摘　　要：目的探讨高糖状态下胰岛素样生长因子1(IGF-1)对大鼠胃平滑肌细胞内质网应激(ERS)及蛋白激酶Cα(PKCα)/蛋白激酶Cβ1(PKCβ1)-钙离子(Ca2+)的影响及意义。方法体外培养原代大鼠胃平滑肌细胞,分为低糖(Con)组、高糖组(HG)、Con+IGF-1组、HG+IGF-1组、HG+PKCβ1抑制剂组(HG+RH)。激光共聚焦显微镜观察各组细胞内Ca2+变化,Western blot法检测葡萄糖调节蛋白78(GRP78)、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)、PKCα、p-PKCα、PKCβ1及p-PKCβ1的表达。结果与Con组比较,HG组GRP78、CHOP、Ca2+浓度、p-PKCβ1/PKCβ1比值升高(P<0.05或P<0.01)。与HG组比较,HG+IGF-1、HG+RH组GRP78、CHOP、Ca2+浓度、p-PKCβ1/PKCβ1降低(P<0.05或P<0.01)。与HG+IGF-1组比较,HG+RH组Ca2+浓度增加(P<0.05)。各组p-PKCα/PKCα比较,差异无统计学意义(P>0.05)。结论高糖状态下IGF-1通过稳定PKCα活性及降低PKCβ1活性下调细胞内Ca2+水平,抑制大鼠胃平滑肌细胞ERS。Objective To investigate the effect and significance of insulin-like growth factor 1(IGF-1)on endoplasmic reticulum stress(ERS)and protein kinase Cα(PKCα)/protein kinase Cβ1(PKCβ1)-calcium ion(Ca2+)in rat gastric smooth muscle cells under high glucose condition.Methods Primary rat gastric smooth muscle cells were cultured in vitro and divided into three groups:common sugar(Con)group,high sugar group(HG),Con+IGF-1 group,HG+IGF-1 group and HG+PKCβ1 inhibitor group(HG+RH).The changes of intracellular Ca2+in each group were observed by laser confocal microscope,and the expressions of glucose regulatory protein 78(GRP78),C/EBP cyclic adenosine monophosphate reaction element binding transcription factor homologous protein(CHOP),PKCα,p-PKCα,PKCβ1 and p-PKCβ1 were detected by Western blot.Results Compared with Con group,GRP78 expression,CHOP expression,Ca2+concentration and p-PKCβ1/PKCβ1 ratio in HG group increased(P<0.05 or P<0.01).Compared with HG group,GRP78 expression,CHOP expression,Ca2+concentration,p-PKCβ1/PKCβ1 ratio in HG+IGF-1 group decreased(P<0.01),while HG+RH group decreased(P<0.05).Compared with HG+IGF-1 group,Ca2+concentration in HG+RH group increased(P<0.05).There was no significant difference in p-PKCα/PKCα ratio between the groups(P>0.05).Conclusion IGF-1 may inhibit ERS in rat gastric smooth muscle cells in a high glucose state by down-regulating the level of Ca2+,with the mechanism stabilizing the activity of PKCα and decreasing the activity of PKCβ1.

关 键 词：高糖 胰岛素样生长因子 胃平滑肌细胞 钙离子 内质网应激 

分 类 号：R587.2[医药卫生—内分泌] R573[医药卫生—内科学]