Xiang Lanting, Zhang Qiongying, Chi Chen, Wu Gu, Lin Zhongmin, Li Jianmin, Gu Qianru, Chen Guorong
1Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang People's Republic of China.
2Department of Pathology, Sir Run Run Shaw Hospital affiliated To Zhejiang University School of Medicine, Hangzhou, Zhejiang People's Republic of China.
Diabetol Metab Syndr. 2020 Jan 7;12:1. doi: 10.1186/s13098-019-0485-z. eCollection 2020.
Diabetes mellitus is an important risk factor for cardiomyopathy. Increasing oxidative stress may be one of the main factors of diabetic cardiomyopathy. A13, a newly synthesized curcumin analog, was proved to be superior to curcumin in biological activity. However, little know about how A13 performed in diabetic models. In this study, we evaluated the ability of curcumin analog A13 to alleviate oxidative stress and ameliorate fibrosis in the myocardium, and explore the underlying mechanisms.
Intraperitoneal injection of streptozotocin (30 mg/kg in 0.1 M sodium citrate buffer, pH 4.5) induced diabetes in high-fat fed rats. The rats were respectively treated with a daily dose of curcumin or A13 via intragastric intubation for 8 weeks. Myocardial tissue sections were stained with hematoxylin-eosin; oxidative stress was detected by biochemical assays; activation of the Nrf2/ARE pathway was detected by Western blot, immunohistochemical staining and RT-qPCR; myocardial fibrosis was identified by Western blot and Masson trichrome staining.
Treatment with curcumin analog A13 reduced the histological lesions of the myocardium in diabetic rats. Curcumin and A13 treatment decreased the malondialdehyde level and increased the activity of superoxide dismutase in the myocardium of diabetic rats. Molecular analysis and immunohistochemical staining demonstrated that dose of 20 mg/kg of A13 could activate the Nrf2/ARE pathway. Molecular analysis and Masson staining showed that curcumin analog A13 treatment significantly ameliorated fibrosis in myocardium of these diabetic rats.
Treatment with curcumin analog A13 protects the morphology of myocardium, restores the MDA levels and SOD activity, activates the Nrf2/ARE pathway and ameliorates myocardial fibrosis in diabetic rats. It may be a useful therapeutic agent for some aspects of diabetic cardiomyopathy.
糖尿病是心肌病的重要危险因素。氧化应激增加可能是糖尿病性心肌病的主要因素之一。A13是一种新合成的姜黄素类似物，其生物学活性被证明优于姜黄素。然而，关于A13在糖尿病模型中的表现知之甚少。在本研究中，我们评估了姜黄素类似物A13减轻心肌氧化应激和改善纤维化的能力，并探讨其潜在机制。
腹腔注射链脲佐菌素（在0.1M柠檬酸钠缓冲液中，pH4.5，30mg/kg）诱导高脂喂养大鼠患糖尿病。通过灌胃分别给予大鼠每日剂量的姜黄素或A13，持续8周。心肌组织切片进行苏木精-伊红染色；通过生化分析检测氧化应激；通过蛋白质免疫印迹法、免疫组织化学染色和逆转录-定量聚合酶链反应检测Nrf2/ARE通路的激活；通过蛋白质免疫印迹法和Masson三色染色鉴定心肌纤维化。
用姜黄素类似物A13治疗可减轻糖尿病大鼠心肌的组织学损伤。姜黄素和A13治疗降低了糖尿病大鼠心肌中的丙二醛水平，提高了超氧化物歧化酶的活性。分子分析和免疫组织化学染色表明，20mg/kg剂量的A13可激活Nrf2/ARE通路。分子分析和Masson染色显示，姜黄素类似物A13治疗可显著改善这些糖尿病大鼠心肌的纤维化。
用姜黄素类似物A13治疗可保护糖尿病大鼠心肌的形态，恢复丙二醛水平和超氧化物歧化酶活性，激活Nrf2/ARE通路并改善心肌纤维化。它可能是治疗糖尿病性心肌病某些方面的有效治疗剂。
