通络熄风汤介导Nrf2/HO-1信号通路改善糖尿病心肌损伤的作用机制

Effect of Tongluo Xifeng Decoction on Nrf2/HO-1 Signaling Pathway Mediated Myocardial Injury in Diabetes

目的:观察通络熄风汤对2型糖尿病模型大鼠心肌细胞损伤的作用及其对核因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路介导的细胞氧化应激的影响。方法:将大鼠分为正常组、模型组及中药组。利用链脲佐菌素(STZ)注射法构建糖尿病大鼠模型。中药组给予中药配方颗粒通络熄风汤悬浮液灌胃治疗,正常组和模型组给予等体积的生理盐水灌胃,连续8周。采用透射电镜观察心肌组织的超微结构。检测超氧化物歧化酶(SOD)和活性氧(ROS)水平;采用蛋白免疫印迹法(Western Blot)和实时荧光聚合酶链式反应(RT-PCR)检测心肌细胞Nrf2/HO-1蛋白及mRNA表达水平。结果:与模型组比较,中药组大鼠体质量及血糖指标改善,差异均有统计学意义(P<0.01)。与模型组比较,中药组大鼠心肌细胞组织超微结构得到恢复,ROS水平降低,SOD水平,Nrf2和HO-1蛋白及mRNA表达升高,差异有统计学意义(P<0.05或P<0.01)。结论:通络熄风汤通过激活Nrf2/HO-1信号减轻心肌组织细胞氧化应激损伤,提高抗氧化酶活性,保护心脏功能。

Objective:To observe the effects of Tongluo Xifeng Decoction on cardiomyocyte injury in rats with type 2 diabetes and its effects on cellular oxidative stress mediated by nuclear factor E2-related factor 2(Nrf2)/hemoglobin oxygenase-1(HO-1) signaling pathway.Methods:The rats were divided into normal group,model group and traditional Chinese medicine group.The diabetic rat model was constructed using streptozotocin(STZ) injection method.The traditional Chinese medicine group was gavaged with the suspension of the traditional Chinese medicine formula granule Tongluo Xifeng Decoction,and the normal group and model group were gavaged with equal volume of saline for 8 consecutive weeks.Transmission electron microscopy was used to observe the ultrastructure of myocardial tissue.The levels of superoxide dismutase(SOD) and reactive oxygen species(ROS) were detected.The levels of Nrf2/HO-1 protein and mRNA in cardiomyocytes were detected by protein immunoblotting(Western Blot) and real-time polymerase chain reaction(RT-PCR).Results:Compared with the model group,body mass and blood glucose indexes of rats in the traditional Chinese medicine group improved,cardiomyocytes of rats and tissue ultrastructure restored,ROS decreased,and the levels of SOD,Nrf2,and HO-1 protein and mRNA increased(P0.05 or P0.01).Conclusion:Tongluo Xifeng Decoction could alleviate oxidative stress injury in myocardial tissue cells by activating Nrf2/HO-1 signal,which improved the activity of antioxidant enzymes and protected cardiac function.