Effect of Zhenwu decoction on cardiomyocyte apoptosis and the PI3K-AKT pathway in rats with congestive heart failure
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1. Jiangxi University of Traditional Chinese Medicine, Nanchang 330000, China. 2. Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006

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R-33

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    Abstract:

    Objective To observe the therapeutic effect of Zhenwu decoction on myocardial pathomorphology and cardiomyocyte apoptosis in rats with heart failure induced by coronary artery ligation, and to explore its effect on apoptosis- related proteins and the PI3K-AKT signaling pathway. Methods At 4 weeks after the operation, surviving rats were randomly divided into six groups with seven rats in each group as follows. (1) Sham operation group: normal saline was administered intragastrically for 28 days at 4 weeks after the operation. (2) model group: normal saline was administered intragastrically for 28 days after 4 weeks. (3) positive control group: 5 mg / kg losartan potassium was administered for 28 days after 4 weeks. ( 4) Zhenwu decoction low dose group: after 4 weeks, 6 g / kg Zhenwu decoction crude drug was administered for 28 days. ( 5 ) Zhenwu decoction middle dose group: 12 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. (6) Zhenwu decoction high dose group: 18 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. Changes in the electrocardiogram, color ultrasound, cardiomyocyte apoptosis, myocardial morphology, PI3K, AKT1 and p-AKT1 protein levels in myocardial tissue, immunohistochemical changes of Bax, Bcl-2, caspase 3, 8, 9 and BNP in the abdominal aorta were observed before and after modeling. Results ( 1) The ST segment of the heart failure model was elevated after coronary artery ligation, indicating that model establishment was successful. (2)The left ventricular mass index and BNP level of heart failure rats were increased significantly, and LVEF and LVFS were decreased significantly, whereas the left the ventricular mass index, BNP level, LVEF and LVFS were improved in the other groups. ( 3) Myocardial fibers in the model group were disordered and broken accompanied by cardiomyocyte swelling, hypertrophy. and inflammatory cell infiltration, which were relieved to various degrees in the other groups. Apoptosis in the model group was significant, which was alleviated after by Zhenwu decoction and positive control group drugs. (4)Compared with the model group, Bcl-2 was increased, and Bax and Caspase 3, 8, 9 were decreased in each treatment group. There was no significant difference in protein expression between Zhenwu decoction middle dose and sham operation groups. (5)Compared with the sham operation group, PI3K, p-AKT1 and AKT1 expression in the model group was increased, and Zhenwu decoction suppressed protein expression of PI3K, p- AKT1 and AKT1. Conclusions Zhenwu decoction reduces cardiomyocyte apoptosis and myocardial pathological changes in HF rats by regulating the PI3K-AKT pathway, enhancing myocardial contractility, and delaying the progression of heart failure.

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History
  • Received:November 01,2021
  • Revised:
  • Adopted:
  • Online: November 09,2022
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