Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Myocardial Injury in Type 2 Diabetic Rats by Regulating Autophagy

Ying Liu, Leilei Ma, Wenxuan Xu, Xiao-jin La, Biwei Zhang, Jianmei Cui, Chunyu Tian, Hong Chang, Ji-an Li
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Abstract

Background: Diabetes mellitus (DM) is a persistent metabolic condition resulting from insufficient insulin or insulin resistance, which gives rise to diverse complications endangering human well-being. Ramulus Mori (Sangzhi) alkaloids ­(SZ-A) have various pharmacological effects, potentially benefiting clinical comprehensive kidney and cardiovascular protection. Nevertheless, the potential protective effect of SZ-A on myocardial injury in individuals with type 2 diabetes mellitus (T2DM) remains unexplored. Materials and Methods: Sprague-Dawley (SD) rats were divided into four groups, including control, model, metformin, and SZ-A. The establishment of the type 2 diabetes model was initiated by injecting streptozotocin (STZ) along with a diet of high glucose and fat. Following a 12-week period of treatment, measurements were taken for heart mass index (HMI), fasting blood glucose (FBG), and 2-h postprandial blood glucose (2hPG). Additionally, serum glycated hemoglobin (HbA1c), indicators of myocardial injury, and oxidative stress were assessed. The expressions of mammalian target of rapamycin (mTOR), p-mTOR, beclin-1, and LC3 in myocardial tissue were detected by Western blot. Results: The administration of SZ-A effectively reduced the levels of HMI, FBG, 2hPG, HbA1c, malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine kinase isoenzymes (CK-MB) in rats with type 2 diabetes while enhancing the activity of superoxide dismutase (SOD). Additionally, SZ-A could improve myocardial tissue arrangement structure and fibrosis degree. Additional analysis revealed that SZ-A suppressed the activation of p-mTOR while enhancing the levels of Beclin-1 and LC3, suggesting that the potential therapeutic impact of SZ-A on myocardial damage could be attributed to its ability to regulate autophagy, thereby mitigating oxidative stress. Conclusion: In summary, the results indicate that SZ-A might possess inhibitory properties against myocardial damage in rats with type 2 diabetes, presenting a potential therapeutic approach in the clinic.
桑枝生物碱(SZ-A)通过调节自噬作用改善 2 型糖尿病大鼠的心肌损伤
背景:糖尿病(DM)是一种因胰岛素不足或胰岛素抵抗而导致的顽固性代谢疾病,会引发多种并发症,危及人类健康。桑枝生物碱(SZ-A)具有多种药理作用,对肾脏和心血管的全面保护具有潜在的临床益处。然而,SZ-A 对 2 型糖尿病(T2DM)患者心肌损伤的潜在保护作用仍有待探索。材料与方法:将 Sprague-Dawley (SD) 大鼠分为四组,包括对照组、模型组、二甲双胍组和 SZ-A 组。通过注射链脲佐菌素(STZ)和高糖高脂饮食建立 2 型糖尿病模型。治疗 12 周后,测量心脏质量指数 (HMI)、空腹血糖 (FBG) 和餐后 2 小时血糖 (2hPG)。此外,还评估了血清糖化血红蛋白(HbA1c)、心肌损伤指标和氧化应激。通过 Western 印迹检测心肌组织中哺乳动物雷帕霉素靶标(mTOR)、p-mTOR、beclin-1 和 LC3 的表达。结果服用 SZ-A 能有效降低 2 型糖尿病大鼠的 HMI、FBG、2hPG、HbA1c、丙二醛(MDA)、乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)的水平,同时提高超氧化物歧化酶(SOD)的活性。此外,SZ-A 还能改善心肌组织的排列结构和纤维化程度。其他分析表明,SZ-A 可抑制 p-mTOR 的激活,同时提高 Beclin-1 和 LC3 的水平,这表明 SZ-A 对心肌损伤的潜在治疗作用可归因于其调节自噬的能力,从而减轻氧化应激。结论总之,研究结果表明,SZ-A 可能具有抑制 2 型糖尿病大鼠心肌损伤的特性,为临床提供了一种潜在的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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