Duan Jialin, Wei Guo, Guo Chao, Cui Jia, Yan Jiajia, Yin Ying, Guan Yue, Weng Yan, Zhu Yanrong, Wu Xiaoxiao, Wang Yanhua, Xi Miaomiao, Wen Aidong
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Am J Chin Med. 2015;43(6):1159-75. doi: 10.1142/S0192415X15500664.
Patients with type 2 diabetes have increased cardiovascular disease risk compared with those without diabetes. Hyperglycemia can induce reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. Our previous study has demonstrated that the total saponins of Aralia taibaiensis (sAT), a frequently-used antidiabetic medicine in traditional Chinese medicine (TCM), can scavenge free radicals in vitro and have good anti-oxidant ability on lipid peroxidation of rat liver microsomes. This work was designed to investigate whether sAT could protect the heart while it was used in the treatment of diabetes. Oxidative stress was induced in H9c2 cells by high glucose (33 mM) and glucose oxidase (15 mU, G/GO) and the protective effects of sAT were evaluated. Treatment of H9c2 cells with G/GO resulted in an increase in cell death, intracellular ROS level and cell oxidative injury, which were markedly reduced by sAT treatment. Further study revealed that sAT induced the nuclear translocation of Nrf2 and expression of its downstream targets. Moreover, Nrf2 siRNA markedly abolished the cytoprotective effects of sAT. sAT exerted cytoprotective effects against oxidative stress induced by hyperglycemia and the cardioprotective effects of sAT might be through the Nrf2/ARE pathway. Thus, sAT might be a promising candidate for the treatment of diabetic cardiomyopathy.
与非糖尿病患者相比，2型糖尿病患者患心血管疾病的风险更高。高血糖会诱导活性氧（ROS）生成，这有助于糖尿病性心肌病的发展。我们之前的研究表明，太白楤木总皂苷（sAT）是一种常用的中药抗糖尿病药物，在体外能够清除自由基，并且对大鼠肝微粒体脂质过氧化具有良好的抗氧化能力。这项研究旨在探究sAT在治疗糖尿病时是否能够保护心脏。通过高糖（33 mM）和葡萄糖氧化酶（15 mU，G/GO）在H9c2细胞中诱导氧化应激，并评估sAT的保护作用。用G/GO处理H9c2细胞会导致细胞死亡增加、细胞内ROS水平升高和细胞氧化损伤，而sAT处理可显著降低这些指标。进一步研究表明，sAT诱导Nrf2核转位及其下游靶点的表达。此外，Nrf2 siRNA显著消除了sAT的细胞保护作用。sAT对高血糖诱导的氧化应激具有细胞保护作用，其心脏保护作用可能通过Nrf2/ARE途径实现。因此，sAT可能是治疗糖尿病性心肌病的一个有前景的候选药物。
