南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (1): 47-54.doi: 10.12122/j.issn.1673-4254.2026.01.05

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石斛合剂通过调控Sirt3介导的线粒体自噬通路缓解大鼠糖尿病心肌病

林心君1(), 何昱霖2, 施红1, 刘佳绣2, 胡海霞3()   

  1. 1.福建中医药大学，中西医结合学院，福建 福州 350122
    2.福建中医药大学，中西医结合研究院，福建 福州 350122
    3.福建中医药大学，科技创新与转化中心，福建 福州 350122
  • 收稿日期:2025-06-10 出版日期:2026-01-20 发布日期:2026-01-16
  • 通讯作者: 胡海霞 E-mail:18960878167@163.com;asunnyhaixia@163.com
  • 作者简介:林心君，博士，教授，E-mail: 18960878167@163.com
  • 基金资助:
    国家自然科学基金(81973827);福建省自然科学基金(2023J01332);福建省自然科学基金(2019J01332);福建中医药大学校管课题(X2022006)

Shihu Mixture alleviates diabetic cardiomyopathy in rats by Sirt3-mediated upregulation of myocardial mitochondrial mitophagy pathway

Xinjun LIN1(), Yulin HE2, Hong SHI1, Jiaxiu LIU2, Haixia HU3()   

  1. 1.College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
    2.Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
    3.Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
  • Received:2025-06-10 Online:2026-01-20 Published:2026-01-16
  • Contact: Haixia HU E-mail:18960878167@163.com;asunnyhaixia@163.com
  • Supported by:
    National Natural Science Foundation of China(81973827)

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摘要：

目的 研究石斛合剂通过Sirt3介导的线粒体自噬通路改善糖尿病心肌病的作用机制。 方法 将40只雄性SPF级SD大鼠分为对照组、模型组、二甲双胍组、石斛合剂组（n=10）。对照组用生理盐水灌胃，其它组用高脂高糖饮食喂养12周和1.0%链脲佐菌素（25 mg/kg）腹腔注射后，模型组用生理盐水继续灌胃，二甲双胍组则用二甲双胍溶液（100 mg·kg-1·d-1）灌胃，石斛合剂组用石斛合剂溶液（16.7 g·kg-1·d-1）灌胃，持续干预4周。给药期间监测空腹血糖和心重指数，应用比色法检测甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、乳酸脱氢酶（LDH）的含量；酶联免疫法检测脑钠肽（BNP）、C反应蛋白（CRP）、α-肿瘤坏死因子（TNF-α）、介素-6（IL-6）的水平；HE及Masson染色观察心脏组织病理改变；应用透射电镜观察心肌细胞的线粒体及自噬体的超微结构；RT-PCR实验检测Sirt3、FoxO3a、PINK1、Parkin、P62、LC3的基因表达水平；Western blotting和免疫组化法检测Sirt3、FoxO3a、p-FoxO3a、PINK1、Parkin、LC3、P62的蛋白表达水平。 结果 与对照组相比，模型组、二甲双胍组和石斛合剂组的空腹血糖、心重指数明显升高（P<0.01），大鼠血清中TC、TG、LDL-C、LDH、CRP、BNP和心肌组织中的TNF-α、IL-6含量显著增加（P<0.01），HDL-C显著降低（P<0.01），心肌纤维排列紊乱，线粒体肿胀溶解，Sirt3、FoxO3a、PINK1、Parkin、LC3的基因表达水平明显下降、P62表达水平升高（P<0.05）；Sirt3、p-FoxO3a/FoxO3a值、PINK1、Parkin、LC3的蛋白表达水平显著降低，P62蛋白水平升高（P<0.05）。与模型组相比，石斛合剂组能显著降低空腹血糖水平和心重指数（P<0.01），同时降低LDH、CRP、BNP、TNF-α、IL-6的含量及TC、TG、LDL-C的水平（P<0.01），升高HDL-C的水平（P<0.01），抑制心肌纤维化，修复线粒体、促使自噬体产生，上调线粒体自噬基因Sirt3、FoxO3a、PINK1、Parkin、LC3（P<0.01），下调P62的基因表达水平（P<0.01），同时升高Sirt3、PINK1、Parkin、LC3蛋白水平和p-FoxO3a/FoxO3a比值（P<0.05），降低P62的蛋白水平（P<0.01）。石斛合剂与二甲双胍组相比差异无统计学意义（P>0.05）。 结论 石斛合剂可能通过Sirt3调节线粒体自噬途径改善糖尿病心肌病的组织损伤及线粒体功能。

关键词: 糖尿病心肌病, 石斛合剂, 线粒体自噬, Sirt3途径

Abstract:

Objective To explore the mechanism of Shihu Mixture (SHM) for improving diabetic cardiomyopathy. Methods Thirty male SD rats were randomized into 3 groups (n=10) for type 2 diabetes mellitus modeling by high-fat and -sugar feeding for 12 weeks and intraperitoneal streptozotocin injection, followed by treatment with daily gavage of normal saline (model group), metformin solution, or SHM extract for 4 weeks, with 10 normally fed rats as the normal control group. Fasting blood glucose and cardiac weight index of the rats were monitored, and their TG, TC, LDL-C, HDL-C, and LDH levels were determined; serum and myocardial levels of BNP, CRP, TNF‑α and IL-6 were detected with ELISA. Myocardial pathological changes and ultrastructures of myocardial mitochondria and autophagosomes were examined with HE and Masson staining and transmission electron microscopy. Myocardial expressions of Sirt3, FoxO3a, PINK1, Parkin, P62, and LC3 mRNAs and proteins were detected with RT-qPCR, Western blotting, and immunohistochemistry. Results Compared with those in the control group, the rats in the other 3 groups showed significantly increased fasting blood glucose, cardiac weight index, serum TC, TG, LDL-C, LDH, CRP and BNP levels and myocardial levels of TNF‑α and IL-6 with lowered HDL-C level, obvious myocardial and mitochondrial pathologies, and dysregulated expression of Sirt3, FoxO3a, p-FoxO3a, PINK1, Parkin, LC3 and P62. Treatment of the rat models with SHM extract significantly reduced fasting blood glucose level and cardiac weight index, lowered the levels of LDH, CRP, BNP, TNF‑α, IL-6, TC, TG, and LDL-C, increased HDL-C level, alleviated myocardial and mitochondrial damages, promoted autophagosome formation, and improved dysregulation of mitochondrial autophagy-related gene expression, showing similar effects to metformin. Conclusion SHM alleviates myocardial damage and improves mitochondrial function in rats with diabetic cardiomyopathy by regulating the mitochondrial autophagy pathway through Sirt3.

Key words: diabetic cardiomyopathy, Shihu Mixture, mitophagy, Sirt3 pathway