摘要
目的探讨中药益糖康是否通过促进沉默信息调节因子2同源体1(silencing information regulatory factor 2 homologous 1,SIRT1)表达调控线粒体稳态,减轻氧化应激诱导的糖尿病db/db小鼠心肌损伤。方法30只糖尿病db/db小鼠适应性饲养1周后随机分3组:模型组、西药组和中药组,每组10只,另取10只正常db/m小鼠作为正常组。给药6周,检测各组小鼠的空腹血糖(fasting blood glucose,FPG)、胰岛素(insulin,INS)、糖化血红蛋白(glycated hemoglobin,HbA1c)、血脂、磷酸激酶同工酶(phosphokinase isoenzyme,CK-MB)、磷酸激酶(phosphokinase,CK)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)及活性氧(reactive oxygen species,ROS)水平,光镜及透射电镜观察心肌组织结构结构变化,免疫组化法及蛋白免疫印迹法(Western blot)检测心肌组织沉默信息调节因子1(SIRT1)、线粒体融合蛋白1(Mfn1)、视神经萎缩蛋白1(Opa1)、动力相关蛋白1(Drp1)、NADPH氧化酶4(NOX4)及超氧化物歧化酶2(SOD2)的表达。结果与正常组比较,模型组的FBG、INS、HOMA-IR、HbA1c、TC、TG、LDL-C、、CK-MB、CK、MDA、ROS水平均显著升高(P<0.01),HDL-C、SOD显著降低(P<0.01),心肌组织病理变化及线粒体损伤显著,SIRT1、Mfn1、Opa1、SOD2蛋白表达水平显著降低(P<0.01),Drp1、NOX4蛋白的表达水平显著升高(P<0.01);与模型组比较,西药组和中药组的FBG、INS、HOMA-IR、HbA1c、TC、TG、LDL-C、CK-MB、CK、MDA、ROS水平均显著降低(P<0.05,P<0.01),HDL-C、SOD显著升高(P<0.05,P<0.01),心肌组织病理及线粒体损伤显著减轻,SIRT1、Mfn1、Opa1、SOD2蛋白表达水平显著升高(P<0.05,P<0.01),Drp1、NOX4蛋白的表达水平显著降低(P<0.01)。结论中药益糖康可通过减少ROS积累减轻氧化应激反应,抑制了糖脂代谢紊乱诱导的心肌损伤,其机制可能与促进SIRT1蛋白表达、调节线粒体融合分裂平衡、调控线粒体稳态从而减少氧化应激反应相关。
Objective To investigate whether Yitangkang(益糖康)regulates mitochondrial homeostasis by promoting the expression of silencing information regulatory factor 2 homologous 1(SIRT1)and alleviates myocardial injury in diabetic db/db mice induced by oxidative stress.Methods Thirty diabetes db/db mice were randomly divided into three groups after adaptive feeding for one week:model group,Western medicine group and Chinese medicine group,with 10 mice in each group,and another 10 normal db/m mice as the normal group.After 6 weeks of administration,the levels of fasting blood glucose(FPG),insulin(INS),glycated hemoglobin(HbA1c),blood lipids,phosphokinase isoenzyme(CK-MB),phosphokinase(CK),malondialdehyde(MDA),superoxide dismutase(SOD)and reactive oxygen species(ROS)of mice in each group were tested.Myocardial tissue structure and mitochondrial ultrastructure were observed under light and transmission electron microscopes.The expressions of SIRT1,Mfn1,Opa1,Drp1,NOX4 and SOD2 proteins in myocardial tissue structure were detected by immunohistochemistry and Western blot.Results Compared with those of the normal group,the levels of FBG,INS,HOMA-IR,HbA1c,TC,TG,LDL-C,CK-MB,CK,MDA and ROS in the model group were significantly increased(P<0.01),while the levels of HDL-C and SOD were significantly reduced(P<0.01).The pathological changes of myocardial tissue and mitochondrial damage were significant.The expression levels of SIRT1,Mfn1,Opa1 and SOD2 proteins were significantly reduced(P<0.01),while the expression levels of Drp1 and NOX4 proteins were significantly increased(P<0.01).Compared with those of the model group,the levels of FBG,INS,HOMA-IR,HbA1c,TC,TG,LDL-C,CK-MB,CK,MDA and ROS in the Western medicine group and the Chinese medicine group were significantly reduced(P<0.05,P<0.01),while the levels of HDL-C and SOD were significantly increased(P<0.05,P<0.01),and myocardial tissue pathology and mitochondrial damage were significantly reduced.The expression levels of SIRT1,Mfn1,Opa1,Drp1,NOX4 and SOD2 proteins were significantly increased(P<0.01),while the expression levels of Drp1 and NOX4 proteins were significantly reduced(P<0.01).Conclusion Yitangkang can reduce oxidative stress by reducing ROS accumulation and inhibit myocardial damage induced by glucose and lipid metabolism disorders.The mechanism may be related to promoting SIRT1 protein expression,regulating mitochondrial fusion and division balance and regulating mitochondrial homeostasis,thereby reducing oxidative stress response.
作者
陈红谨
杨宇峰
庞敏
石岩
CHEN Hongjin;YANG Yufeng;PANG Min;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Shanxi University of Traditional Chinese Medicine,Jinzhong 030619,Shanxi,China;Liaoning Province Chinese Medicine Research Institute,Shenyang 110034,Liaoning,China)
出处
《辽宁中医杂志》
北大核心
2025年第8期182-187,I0004,I0005,共8页
Liaoning Journal of Traditional Chinese Medicine
基金
国家中医药领军人才支持计划-岐黄学者项目(国中医药人教发[2018]12)
辽宁省中央引导地方科技发展专项(2019JH6/10100009)
全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号)。
