Mohammadi Mohammad, Salehi Amir Mohammad, Azadi Samaneh Mohassel, Khajvand-Abedini Maryam, Nazari-Serenjeh Farzaneh, Habibi Parisa
Department of Medical Laboratory Science, Faculty of Medicine, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran.
Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.
Antiinflamm Antiallergy Agents Med Chem. 2025;24(2):103-113. doi: 10.2174/0118715230305886240916105248.
This study aimed to investigate the effects of genistein, swimming exercise, and their co-treatment on heart oxidative stress, inflammation, and cardiomyopathy in ovariectomized diabetic rats.
It is well-established that diabetes is a major risk factor for cardiovascular disease in both young and postmenopausal women. Genistein is a natural phytoestrogen that has estrogenic effects. Studies have shown that genistein has a positive impact on menopause, cardiovascular disease, and diabetes in women. However, the impact of genistein treatment alone and in combination with exercise training on the management of cardiac disease in diabetic women after ovarian hormone deprivation has not been fully explored.
The objective of this study was to evaluate the effect of genistein alone or in combination with exercise training on the cardiac expression of oxidative/inflammation biomarkers (MDA, OSI, TOS, TNF- α, and NF-κB) and miRNA-133, IGF-1, and Bcl-2 in the diabetic ovariectomized rats.
A group of Wistar rats were randomly divided into seven groups, with eight rats in each group. The groups were named control, sham, ovariectomized group (OVX), OVX +diabetes (OD), OD+ genistein (1 mg/kg, eight weeks; daily SC), OD+exercise (eight weeks), and OD+ genistein+exercise (eight weeks). The rats were given a high-fat diet and low-dose streptozotocin injection to induce diabetes. After eight weeks, the rats were anesthetized, and their hearts were removed. The study assessed the effects of treatment by measuring the expression of miRNA-133 using Real-time Polymerase Chain Reaction (PCR) and the protein levels of Bcl-2, Bax, and IGF- 1 using Western blotting. The study also evaluated the levels of inflammation and oxidative stress markers using ELISA. Pathological changes were also assessed using periodic acid Schiff and hematoxylin & eosin.
After ovariectomy, the levels of cardiac miRNA-133, IGF-1, and Bcl-2 expression were down-regulated, and the levels of MDA, OSI, TOS, TNF-α, and NF-κB were increased, with a reduced total antioxidant capacity. Diabetes had an additive effect on these factors. Genistein was found to have a positive impact on oxidative and inflammation levels, and it also increased the expression of miRNA-133, Bcl-2, and IGF-1 in rats with OD. Furthermore, the combination of genistein and exercise had a positive effect on miRNA-133, Bcl-2, and IGF-1 expression in the heart, leading to a decrease in Bax levels. The combined intervention showed a noticeable improvement in oxidative and inflammation conditions. Histological examination revealed some abnormalities in cardiac tissue, which were found to be improved with genistein and/or exercise treatments.
Genistein or/and exercise as a natural replacement therapy could improve diabeticinduced cardiac complications in ovariectomized rats' hearts.
本研究旨在探讨金雀异黄素、游泳运动及其联合治疗对去卵巢糖尿病大鼠心脏氧化应激、炎症和心肌病的影响。
众所周知，糖尿病是年轻女性和绝经后女性心血管疾病的主要危险因素。金雀异黄素是一种具有雌激素作用的天然植物雌激素。研究表明，金雀异黄素对女性的更年期、心血管疾病和糖尿病有积极影响。然而，单独使用金雀异黄素以及与运动训练联合使用对卵巢激素缺乏后糖尿病女性心脏病管理的影响尚未得到充分研究。
本研究的目的是评估单独使用金雀异黄素或与运动训练联合使用对去卵巢糖尿病大鼠心脏氧化/炎症生物标志物（丙二醛、氧化应激指数、总氧化应激、肿瘤坏死因子-α和核因子-κB）以及微小RNA-133、胰岛素样生长因子-1和Bcl-2表达的影响。
将一组Wistar大鼠随机分为七组，每组八只。这些组分别命名为对照组、假手术组、去卵巢组（OVX）、去卵巢+糖尿病组（OD）、OD+金雀异黄素组（1mg/kg，八周；每日皮下注射）、OD+运动组（八周）和OD+金雀异黄素+运动组（八周）。给大鼠喂食高脂饮食并注射低剂量链脲佐菌素以诱导糖尿病。八周后，将大鼠麻醉并取出心脏。该研究通过实时聚合酶链反应（PCR）测量微小RNA-133的表达以及使用蛋白质印迹法测量Bcl-2、Bax和胰岛素样生长因子-1的蛋白质水平来评估治疗效果。该研究还使用酶联免疫吸附测定法评估炎症和氧化应激标志物的水平。还使用过碘酸希夫染色法和苏木精-伊红染色法评估病理变化。
去卵巢后，心脏微小RNA-133、胰岛素样生长因子-1和Bcl-2的表达水平下调，丙二醛、氧化应激指数、总氧化应激、肿瘤坏死因子-α和核因子-κB的水平升高，总抗氧化能力降低。糖尿病对这些因素有叠加作用。发现金雀异黄素对氧化和炎症水平有积极影响，并且还增加了OD大鼠中微小RNA-133、Bcl-2和胰岛素样生长因子-1的表达。此外，金雀异黄素和运动的联合对心脏中微小RNA-133、Bcl-2和胰岛素样生长因子-1的表达有积极影响，导致Bax水平降低。联合干预在氧化和炎症状况方面显示出明显改善。组织学检查显示心脏组织存在一些异常，发现金雀异黄素和/或运动治疗可改善这些异常。
金雀异黄素或/和运动作为一种天然替代疗法可以改善去卵巢大鼠心脏中糖尿病诱导的心脏并发症。
