二甲双胍对妊娠期糖尿病大鼠MEK/ERK通路及心肌凋亡的影响  

Effect of metformin on MEK/ERK pathway and myocardial apoptosis in gestational diabetes mellitus rats

作　　者：邢少宁 符爱贞 程虹[1] 周娃娃 林和先 Xing Shaoning;Fu Aizhen;Cheng Hong;Zhou Wawa;Lin Hexian(The department of obstetrics and gynecology,Haikou City Maternal and Child Health Hospital,Haikou 570203,China)

机构地区：[1]海口市妇幼保健院妇产科,海口570203

出　　处：《广西医科大学学报》2023年第2期254-261,共8页Journal of Guangxi Medical University

基　　金：海南省卫生健康行业科研项目资助(No.20A200076)。

摘　　要：目的:研究二甲双胍对妊娠期糖尿病大鼠MEK/ERK通路及心肌凋亡的影响。方法:构建妊娠期糖尿病大鼠模型。将实验大鼠分为正常对照组、模型对照组、二甲双胍处理组,每组12只。二甲双胍处理组大鼠每日腹腔注射70 mg/kg的二甲双胍。采用ELISA试验、苏木精—伊红染色法(HE染色)、Tunel、实时荧光定量聚合酶链式反应(RT-qPCR)、蛋白印迹法(western blotting)法及超声心动图分别检测各组大鼠的血清中血清乳酸脱氢酶(LDH)、肌钙蛋白(cTnI)、肌酸激酶心型同工酶(CKMB)含量水平、心肌组织中超氧化物歧化酶(SOD)、丙二酫(MDA)及一氧化氮(NO)水平、心肌组织凋亡水平、凋亡相关基因和蛋白、心脏功能、心肌形态学及二甲双胍对大鼠MEK/ERK通路的影响。结果:与正常对照组相比,模型对照组大鼠血清中LDH、cTnI、CK-MB含量显著上升(P<0.05)。与模型对照组相比,二甲双胍处理组血清中LDH、cTnI、CK-MB含量显著降低(P<0.05);二甲双胍显著改善了大鼠心肌形态学,降低了炎症细胞浸润,改善了心肌细胞变性、水肿;与正常对照组相比,模型对照组大鼠心肌组织中凋亡细胞数量显著上升。与模型对照组相比,二甲双胍处理组大鼠心肌组织中凋亡细胞数量显著降低;与正常对照组相比,模型对照组大鼠心肌组织中Bax/Bcl2、active-caspase 3及active-caspase 9水平显著上升(P<0.05)。与模型对照组相比,二甲双胍处理组大鼠心肌组织中Bax/Bcl2、active-caspase 3及active-caspase 9水平显著降低(P<0.05);超声心动图结果表明二甲双胍显著改善了大鼠心脏功能;与正常对照组相比,模型对照组大鼠心肌组织中p-MEK/MEK、p-ERK1/2/ERK1/2、SIRT1蛋白相对表达量显著降低(P<0.05)。与模型对照组相比,二甲双胍处理组大鼠心肌组织中p-MEK/MEK、pERK1/2/ERK1/2蛋白相对表达量显著上升(P<0.05);与正常对照组相比,大鼠心肌组织中SOD、NO水平显著降低,而MDObjective:To study the effect of metformin on MEK/ERK pathway and myocardial apoptosis in rats with gestational diabetes mellitus.Methods:The rat model of gestational diabetes mellitus was established.The experimental rats were divided into normal control group,model control group and metformin treatment group,with 12 rats in each group.Metformin treatment group rats were intraperitoneally injected with 70 mg/kg metformin every day.ELISA test,hematoxylin-eosin(HE)staining,Tunel,real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),western blotting and echocardiography were used to detect serum lactate dehydrogenase(LDH),cardiac troponin I(cTnI),creatine kinase isoenzyme-MB(CK-MB)levels in serum,superxide dismutase(SOD)in myocardial tissue,malondialdehyde(MDA)and nitric oxide(NO)level,heart apoptosis level of muscle tissue,apoptosis-related genes and proteins,cardiac function and myocardial morphology,and the effect of metformin on MEK/ERK pathway in rats in each group.Results:Compared with normal control group,the contents of LDH,cTnI and CK-MB in serum of rats in model control group significantly increased(P<0.05).Compared with model control group,the contents of LDH,cTnI and CK-MB in serum of metformin treatment group significantly decreased(P<0.05).Metformin significantly improved the morphology of rat myocardium,reduced the infiltration of inflammatory cells,and improved the degeneration and edema of myocardial cells.Compared with normal control group,the number of apoptotic cells in myocardial tissue of rats in model control group increased significantly.Compared with the model control group,the number of apoptotic cells in the myocardial tissue of rats in metformin treatment group decreased significantly.Compared with normal control group,the levels of Bax/Bcl2,active-caspase 3 and active-caspase 9 in myocardial tissue of rats in model control group significantly increased(P<0.05).Compared with model control group,the levels of Bax/Bcl2,active-caspase 3 and active-caspase 9 significantly de

关 键 词：二甲双胍 妊娠期糖尿病大鼠 心肌凋亡 

分 类 号：R587.1[医药卫生—内分泌]