EGCG抗糖尿病心肌病小鼠心肌组织中氧化应激损伤作用机制的探讨

Anti-inflammatory and Anti-oxidative Stress Damage of Catechin Gallate on Diabetic Myocardial in C57 Mice

目的：探讨儿茶素没食子酸酯（EGCG）对糖尿病小鼠高糖诱导的心肌组织氧化应激损伤的影响。方法：采用雄性C57小鼠给予高糖高脂饮食6周后,按70 mg·kg^-1的标准腹腔注射链脲佐菌素（STZ）,连续5 d。空腹血糖（FBG）〉16.7 mmol·L^-1视为造模成功。后随机分为空白组,模型组,EGCG低、中、高剂量组（50,100,200 mg·kg^-1）,N-乙酰半胱氨酸（NAC,100 mg·kg^-1）组,腹腔注射,隔天1次,连续4周。分别测定小鼠体重、心脏质量、心脏质量指数、血糖值;镜下观察心肌细胞及组织病理变化;酶联免疫吸附法（ELISA）检测心肌组织活性氧（ROS）,超氧化物歧化酶（SOD）,丙二醛（MDA）及炎性因子白细胞介素（IL）-1β,IL-6,肿瘤坏死因子（TNF）-α的含量;蛋白免疫印迹法（Western blot）测定心肌组织中NF-E2相关因子2（Nrf2）介导的抗氧化通路中血红素氧合酶-1（HO-1）和醌氧化还原酶1（NQO1）的表达。结果：与模型组相比,EGCG（100 mg·kg^-1）组能一定程度降低血清中的FBG水平（P〈0.05）;抑制心肌细胞肥大及心肌组织纤维化程度,增强SOD活性,降低MDA,ROS含量（P〈0.05）;降低组织中炎性因子IL^（-1）β,IL-6,TNF-α的含量（P〈0.05）;激活心肌细胞核内Nrf2介导的抗氧化通路,作用优于强抗氧化剂NAC。结论：EGCG对高糖诱导的心肌细胞损伤具有保护作用,其机制可能与EGCG的抗氧化应激、抗炎作用有关。

Objective： To explore the protective effect of catechin gallate（EGCG） on diabetic myocardial injury in C57 mice. Method： The diabetic cardiomyopathy injury model in C57 mice was induced by injected with streptozocin（STZ,70 mg·kg^-1） and provided with high-diet food. The DCM mice were randomly divided into 6 groups,namely blank group,model group,EGCG group（50,100,200 mg·kg^-1）,and N-acetyl-Lcysteine（NAC） group（100 mg·kg^-1）. Each group was put to death on the 14 thday after intraperitoneal injection. The level of fasting blood-glucose（FBG） was detected by kit; reactive oxygen（ROS）,malondialdehyde（MDA）,superoxide dismutase（SOD）,interniukin（IL）-1β,IL-6 and tumor necrosis factor（TNF）-α were measured by enzyme linked immunosorbent assay（ELISA） kit. Myocardial pathological changes of cardiomyopathy injury were observed under microscope; Nrf2 and HO-1,NQO1 protein kinases were detected by Western blot.Result： Compared with the model group,EGCG（100 mg·kg^-1） can decrease the level of FBG in DCM C57 mice and inhibit the activities of IL^（-1）β,IL-6,MDA,ROS in cardiac muscle tissues（P〈0. 05）; increase the activity of SOD in cardiac muscle tissues（P〈0. 05）; increase the expression of protein kinase of Nrf2,HO-1,NQO1 in cardiac muscle tissues（P〈0. 05）. Moreover,EGCG（100 mg·kg^-1） can restrain the cardiomyocyte hypertrophy and interstitial fibrosis apparently in cardiac muscular tissues. The findings showed that EGCG was better than NAC. Conclusion： EGCG has a protective effect on diabetic cardiomyopathy in C57 mice. The mechanism may be correlated with its anti-inflammatory and anti-oxidative stress damage action.