心梗后心衰大鼠模型中SIRT1/PGC-1α信号通路及葡萄糖代谢酶表达变化  

Changes of glucose metabolizing enzyme expression with SIRT1/PGC-1αsignaling pathway in rat model of heart failure after myocardial infarction

作　　者：文丹 黄丹丹 孙梁 孙雨婷 李叶丽 王羽 杨丹莉 Wen Dan;Huang Dandan;Sun Liang;Sun Yuting;Li Yeli;Wang Yu;Yang Danli(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563006,China;School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563006,China;School of Public Health,Inner Mongolia Minzu University,Tongliao Inner Mongolia 028043,China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563006 [2]遵义医科大学药学院,贵州遵义563006 [3]内蒙古民族大学公共卫生学院,内蒙古通辽028043

出　　处：《遵义医科大学学报》2025年第1期1-8,共8页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82260782)。

摘　　要：目的基于SIRT1/PGC-1α信号通路研究冠状动脉结扎所致大鼠心肌梗死(MI)后心力衰竭(HF)动物模型中葡萄糖代谢酶表达的变化。方法将SD大鼠随机分为假手术组(Sham,n=10)和模型组(Model,n=10)。采用小动物超声检测仪检测大鼠左心功能,观察射血分数(EF)、短轴缩窄率(FS)、左心室收缩末期前壁厚度(LVAWs)、左心室收缩末期后壁厚度(LVPWs)、心输出量(CO)、心搏量(SV)、左心室收缩末期容积(LVESV)以及左心室收缩末期内径(LVIDs)的变化。采用苏木精-伊红(HE)染色观察大鼠左心室组织病理变化。采用Western blot检测大鼠左心室组织中β-肌球蛋白重链(β-MHC)、沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、沉默信息调节因子3(SIRT3)及己糖激酶2(HK2)、乳酸脱氢酶A(LDHA)、丙酮酸脱氢酶E1(PDH E1)、异柠檬酸脱氢酶2(IDH2)和琥珀酸脱氢酶A(SDHA)的表达。采用比色法检测大鼠血清中L-乳酸的含量。结果大鼠MI后HF模型中EF、FS、CO、SV、LVAWs和LVPWs降低,LVESV和LVIDs增加(P<0.05);左心室间质纤维化和炎性细胞浸润;β-MHC蛋白表达上调(P<0.001);SIRT1、PGC-1α、SIRT3、HK2、LDHA、PDH E1、IDH2及SDHA糖代谢相关蛋白表达下调(P<0.05);血清中L-乳酸含量增加(P<0.001)。结论大鼠MI后HF模型中SIRT1、PGC-1α、SIRT3、HK2、LDHA、PDH E1、IDH2及SDHA蛋白表达下调,引起心肌葡萄糖的能量利用发生障碍,促进心功能降低和心室重构发生。Objective To study the changes of glucose metabolizing enzyme in heart failure(HF)rat model after myocardial infarction(MI)induced by coronary artery ligation with SIRT1/PGC-1αsignaling pathway.Methods SD rats were randomly divided into Sham group(n=10)and Model group(n=10).The cardiac function of rats was detected by small animal ultrasonic detector.The changes of ejection fraction(EF),short-axis coarctation rate(FS),left ventricular anterior wall end-systolic thickness(LVAWs),left ventricular posterior wall end-systolic thickness(LVPWs),cardiac output(CO),stroke volume(SV),left ventricular end-systolic volume(LVESV)and left ventricular end-systolic diameter(LVIDs)were observed.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of left ventricular tissue in rats.Western blot was adopted to analyze the changes ofβ-myosin heavy chain(β-MHC),silent information regulators(SIRT1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),silencing message regulator 3(SIRT3),hexokinase 2(HK2),lactate dehydrogenase A(LDHA),acetone acid pyruvate dehydrogenase E1(PDH E1),isocitrate dehydrogenase 2(IDH2)and succinate dehydrogenase A(SDHA)in rat’s left ventricular tissue.Results Compared with Sham group,EF,FS,CO,SV,LVAWs and LVPWs were decreased,while LVESV and LVIDs were increased(P<0.05);Interstitial fibrosis and inflammatory cell infiltration were observed for the left ventricular;β-MHC protein expression was up-regulated(P<0.001);SIRT1,PGC-1αand SIRT3 proteins expression were down-regulated;expression of glucose metabolism-related proteins such as HK2,LDHA,PDH E1,IDH2 and SDHA were down-regulated(P<0.05);Serum L-lactic acid content was increased(P<0.001)in rat HF model after MI.Conclusion The down-regulation SIRT1/PGC-1αsignaling pathway and the decreased expression of HK2,LDHA,PDH E1,IDH2 and SDHA proteins lead to the dysfunction of myocardial glucose utilization,which aggravates the impaired cardiac function and ventricular remodeling in rat model of HF after MI.

关 键 词：心力衰竭 沉默信息调节因子1 过氧化物酶体增殖物激活受体γ共激活因子1α 葡萄糖代谢酶 

分 类 号：Q493.4[生物学—生理学]