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通脉降糖胶囊减轻大鼠糖尿病心肌病发展过程中的心肌氧化应激和纤维化。

Tongmai Hypoglycemic Capsule Attenuates Myocardial Oxidative Stress and Fibrosis in the Development of Diabetic Cardiomyopathy in Rats.

作者信息

Zeng Jie-Qiong, Zhou Hui-Fen, Du Hai-Xia, Wu Yu-Jia, Mao Qian-Ping, Yin Jun-Jun, Wan Hai-Tong, Yang Jie-Hong

机构信息

College of Basic Medicine Sciences, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310051, China.

College of Life Science, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310051, China.

出版信息

Chin J Integr Med. 2025 Mar;31(3):251-260. doi: 10.1007/s11655-024-4002-3. Epub 2024 Dec 7.

DOI:10.1007/s11655-024-4002-3
PMID:39644459
Abstract

OBJECTIVE

To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats.

METHODS

A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively.

RESULTS

Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01).

CONCLUSION

THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.

摘要

目的

探讨通脉降糖胶囊(THC)对糖尿病心肌病(DCM)大鼠心肌损伤的影响。

方法

将24只Sprague Dawley大鼠用高脂高糖饲料喂养4周,然后腹腔注射链脲佐菌素以建立DCM模型。另外,选取6只饮食正常的大鼠作为对照组。造模后,通过计算机随机数字法将24只DCM大鼠随机分为模型组、低剂量THC组、中剂量THC组和高剂量THC组,每组6只,分别采用灌胃给予0、0.16、0.32、0.64 g/kg的THC。给予THC 12周后,分别采用超声心动图、组织病理学染色、生化分析及蛋白质免疫印迹法检测心肌结构、氧化应激(OS)、生化指标、心肌纤维化蛋白表达及核因子红细胞2相关因子2(Nrf2)元件的变化。

结果

THC治疗可显著降低肌酸激酶、乳酸脱氢酶、肌酸激酶同工酶等心肌标志物水平(P<0.01);提高心率、射血分数、心输出量、舒张期室间隔厚度等心功能指标(P<0.05或P<0.01);降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、天冬氨酸转氨酶等生化指标水平(P<0.05或P<0.01);降低心肌纤维化标志物α-平滑肌肌动蛋白(α-SMA)和I型胶原(Col-1)蛋白水平(P<0.01),改善心肌形态及心肌间质纤维化状态。THC可显著降低模型大鼠丙二醛水平(P<0.01),提高过氧化氢酶、超氧化物歧化酶和谷胱甘肽水平(P<0.01),并显著提高大鼠左心室Nrf2、NAD(P)H:醌氧化还原酶1、血红素加氧酶-1和超氧化物歧化酶2蛋白的表达(P<0.01)。

结论

THC激活Nrf2信号通路,对减轻DCM大鼠的OS损伤和心脏纤维化起保护作用。

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