Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Islamic Republic of Iran.
Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Islamic Republic of Iran; Department of Physiology, School of Medicine, Neurophysiology Research Center, Hamedan University of Medical Sciences, Hamedan, Islamic Republic of Iran.
Biomed Pharmacother. 2022 Sep;153:113411. doi: 10.1016/j.biopha.2022.113411. Epub 2022 Jul 19.
Myocardial disorders are the most common cause of renal failure and mortality in diabetic patients, but the molecular mechanism of this process is not yet clear. The reduction of nuclear Erythroid2-related factor-2 (Nrf-2) and positive regulators of Nrf-2 proteins, such as DJ-1 and microRNA-126 (miR-126), after hypoxia and the promotion of reactive oxygen species, might be an intervention indicator in renal failure after myocardial ischemia-reperfusion. Therefore, this study evaluates the renoprotective effect of exercise training and Crataegus persica extract (CE) on myocardial ischemia-reperfusion-induced kidney injury in diabetic rats. Fifty rats were divided into five groups: healthy sedentary control (Con), sedentary diabetic (D), interval trained diabetic (TD), diabetic plus Crataegus persica extract treatment (CD), and interval trained diabetic plus Crataegus persica extract treatment (TCD) groups. The rats in the exercise groups were subjected to moderate-intensity interval training five days per week for ten weeks. The rats in CD and TCD groups received 300 mg/kg of Crataegus persica through gavage for ten weeks. Then, the subjects underwent 30 min of myocardial ischemia and subsequently reperfusion for 24 h. At the end of the experiment, insulin sensitivity, oxidative stress, renal function, histopathology of the kidney, Nrf-2, miR-126, and DJ-1 gene expression levels were evaluated. The results show that the treatments decreased elevated levels of renal oxidative stress, glomerular filtration rate, insulin sensitivity, and pathological score in diabetic rats. Also, the expression of Nrf-2 and miR-126, unlike DJ-1, decreased in diabetic rats due to interval training. Due to the results, diabetes aggravates acute myocardial ischemia-reperfusion-induced kidney injury, while moderate-intensity interval training and Crataegus persica treatment simultaneously ameliorate myocardial ischemia-reperfusion-induced renal injury via miR-126/Nrf-2 pathway and improve insulin sensitivity and renal function in type 1 diabetic rats.
心肌障碍是糖尿病患者肾衰竭和死亡的最常见原因，但这一过程的分子机制尚不清楚。缺氧后核红细胞 2 相关因子 2（Nrf-2）和 Nrf-2 蛋白的正调控因子，如 DJ-1 和 microRNA-126（miR-126）的减少，以及活性氧的产生，可能是心肌缺血再灌注后肾衰竭的干预指标。因此，本研究评估了运动训练和山楂提取物（CE）对糖尿病大鼠心肌缺血再灌注引起的肾损伤的保护作用。将 50 只大鼠分为五组：健康安静对照组（Con）、安静糖尿病组（D）、间歇训练糖尿病组（TD）、糖尿病加山楂提取物治疗组（CD）和间歇训练糖尿病加山楂提取物治疗组（TCD）。运动组大鼠每周进行 5 天中等强度间歇训练，共 10 周。CD 和 TCD 组大鼠连续 10 周灌胃给予 300mg/kg 山楂提取物。然后，所有大鼠均进行 30min 的心肌缺血，随后再灌注 24h。实验结束时，评估胰岛素敏感性、氧化应激、肾功能、肾脏组织病理学、Nrf-2、miR-126 和 DJ-1 基因表达水平。结果表明，这些治疗可降低糖尿病大鼠升高的肾氧化应激、肾小球滤过率、胰岛素敏感性和病理评分。此外，与 DJ-1 不同，由于间歇训练，糖尿病大鼠的 Nrf-2 和 miR-126 表达降低。由于这些结果，糖尿病加重急性心肌缺血再灌注引起的肾损伤，而中等强度间歇训练和山楂提取物治疗通过 miR-126/Nrf-2 途径同时改善 1 型糖尿病大鼠的心肌缺血再灌注引起的肾损伤，并改善胰岛素敏感性和肾功能。
