背景:氧化应激可能导致糖尿病心肌病的心脏ryanodine受体(RyR2)功能障碍。人参皂苷Rb1(Rb1)是人参治疗心血管疾病的主要药理活性成分。Rb1是否治疗糖尿病心脏损伤仍然未知。本研究旨在探讨Rb1对糖尿病损伤心肌组织的影响,并进一步探讨其可能的分子药理学机制。
方法:雄性SD大鼠注射链脲佐菌素溶液2周,随后6周Rb1或胰岛素治疗。SOD的活性,CAT,Gpx,并测量MDA水平;组织学和超微结构分析,进行RyR2活性和磷酸化RyR2(Ser2808)蛋白表达分析;和Tunel测定。
结果:SOD活性降低,CAT,糖尿病组的Gpx和MDA水平高于对照组。Rb1处理增加了SOD的活性,CAT,与糖尿病大鼠相比,Gpx和MDA水平降低。中和RyR2活性在糖尿病中明显低于对照组,Rb1治疗组较糖尿病组增加。与对照组相比,糖尿病大鼠RyR2Ser2808的磷酸化表达增加,并用胰岛素和Rb1治疗减毒。糖尿病细胞凋亡率增加,Rb1处理降低了细胞凋亡率。Rb1和胰岛素改善糖尿病大鼠心肌损伤。
结论:这些数据表明Rb1可用于减轻氧化损伤,糖尿病心肌病患者RyR2Ser2808磷酸化降低,心肌细胞凋亡率降低。
BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms.
METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed.
RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats.
CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.