Zhang Xu, Ke Pei-Xiong, Yuan Xun, Zhang Gui-Ping, Chen Wen-Liang, Zhang Gen-Shui
Key Laboratory of Molecular Clinical Pharmacology & Guangzhou Institute of Cardiovascular Disease, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Department of Biology, York University, 4700 Keele Street, Toronto, ON, Canada M3J 1P3.
Biomed Res Int. 2021 Jan 29;2021:8881843. doi: 10.1155/2021/8881843. eCollection 2021.
Diabetic cardiomyopathy is one of the cardiac complications in diabetes patients, eventually resulting in heart failure and increasing morbidity and mortality. Oxidative stress is a critical pathological feature in diabetic hearts, contributing to the development of DCM. Forskolin (FSK) was shown to reduce oxidative stress. This study was aimed at investigating the effects of FSK on diabetic hearts and the relevant molecular mechanisms.
Streptozotocin- (STZ-) induced diabetes in mice was treated with FSK through intraperitoneal injection. Cardiac functions were evaluated by echocardiography. Hematoxylin-eosin and Masson trichrome staining was employed to determine heart morphological changes and cardiac fibrosis, respectively. Cardiac fibrosis-related markers were detected by western blot. Superoxide dismutase activity, reduced/oxidized glutathione ratio, and malondialdehyde concentration in left ventricles were determined using respective commercial kits.
Abnormal cardiac diastolic dysfunction and cardiac fibrosis were observed in diabetic hearts. FSK treatment significantly improved the cardiac diastolic function and attenuated the abnormal morphological change in diabetic hearts. Moreover, FSK treatment in diabetic mice decreased the expression of fibronectin, collagen I, TGF-, and -SMA and reduced myocardial fibrosis. Furthermore, we observed that FSK significantly blocked oxidative stress in diabetic hearts.
Our study demonstrates that FSK protects against the development of DCM in STZ-induced diabetes in mice. Our study suggests that FSK might be a potential target for drug development in treating DCM.
糖尿病性心肌病是糖尿病患者的心脏并发症之一，最终会导致心力衰竭，并增加发病率和死亡率。氧化应激是糖尿病心脏的一个关键病理特征，促进了糖尿病性心肌病的发展。已表明福斯高林（FSK）可减轻氧化应激。本研究旨在探讨FSK对糖尿病心脏的影响及相关分子机制。
通过腹腔注射FSK治疗链脲佐菌素（STZ）诱导的小鼠糖尿病。采用超声心动图评估心脏功能。分别采用苏木精-伊红染色和Masson三色染色来确定心脏形态变化和心脏纤维化。通过蛋白质免疫印迹法检测心脏纤维化相关标志物。使用相应的商业试剂盒测定左心室超氧化物歧化酶活性、还原型/氧化型谷胱甘肽比值和丙二醛浓度。
在糖尿病心脏中观察到心脏舒张功能异常和心脏纤维化。FSK治疗显著改善了心脏舒张功能，并减轻了糖尿病心脏的异常形态变化。此外，对糖尿病小鼠进行FSK治疗可降低纤连蛋白、I型胶原、转化生长因子和α-平滑肌肌动蛋白的表达，并减少心肌纤维化。此外，我们观察到FSK显著阻断了糖尿病心脏中的氧化应激。
我们的研究表明，FSK可预防STZ诱导的小鼠糖尿病中糖尿病性心肌病的发展。我们的研究表明，FSK可能是治疗糖尿病性心肌病药物开发的一个潜在靶点。
