Mechanism Study on the Inhibition of Myocardial Fibrosis in AS Model Rats through cAMP/PKA/PPARγ Signalling Pathway by the Traditional Chinese Medicine Ciwujia
GAO Jing, LIU Yang, et al
Shengjing Hospital Affiliated to China Medical University, Liaoning Shenyang 11000,China
Abstract：Objective: To investigate the mechanism by which Ciwujia inhibits myocardial fibrosis in AS model rats through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/peroxisome proliferator activated receptor gamma (PPAR gamma) signaling axis. Methods: A total of 44 SPF grade Wistar rats were selected for 6 weeks and randomly divided into a control group, a model group, a simvastatin group, and a Ciwujia group. In addition to the control group, the model group, simvastatin group and acanthopanax senticosus group were fed with high-fat diet combined with intraperitoneal injection of vitamin D3 to establish atherosclerosis (AS) model. After successful model replication, the control group and model group were given 5ml of physiological saline by gavage, the simvastatin group was given simvastatin solution by gavage, and the Ciwujia group was given a Ciwujia medicinal solution by gavage, with continuous intervention for 4 weeks. After the intervention, a small animal ultrasound machine was used to detect the rat heart for cardiac ultrasound examination. The length of the tibia (TL) was measured. The Heart Mass Index (HMI), Left Ventricular Mass Index (LVMI), and Lung Mass Index (LMI), as well as the ratio of heart mass to tibial length (HM/TL), left ventricular mass to tibial length (LV/TL), and lung mass to tibial length (LM/TL) were measured; HE staining was used to observe myocardial morphology, while Masson staining was used to observe the degree of myocardial fibrosis; TUNEL method was used to detect myocardial cell apoptosis; Immunofluorescence method was used to detect the positive expression of cAMP and PKA. Western blot technology was used to detect the expression of cAMP PKA signaling pathway related proteins. Results: Compared with the model group, the simvastatin group showed an increase in LVEF and LVFS (P<0.05), a significant decrease in HMI, LVMI, LMI, HM/TL, LV/TL, and LM/TL (P<0.05), a decrease in myocardial cell apoptosis rate (P<0.05), an increase in cAMP, PKA, and PPAR γ positive expression in myocardial tissue (P<0.05), and a decrease in MMP-9, TIMP-1, α - SMA, TGF- β1, ColI, and ColIII protein expression in myocardial tissue (P<0.05); Compared with the simvastatin group, the levels of LVEF and LVFS in the Ciwujia group were higher (P<0.05), while the levels of HMI, LVMI, LMI, HM/TL, LV/TL, and LM/TL were lower (P<0.05). The apoptosis rate of myocardial cells was lower (P<0.05), and the expression levels of cAMP, PKA, and PPAR γ in myocardial tissue were higher (P<0.05). The expression levels of MMP-9, TIMP-1, α - SMA, TGF-β1, ColI, and ColIII proteins in the myocardial tissue of rats in the Ciwujia group were lower (P<0.05). Conclusion: Ciwujia can inhibit the differentiation of cardiac fibroblasts and reduce the excessive accumulation of type I/III collagen fibers by activating the cAMP/PKA/PPAR γ signaling pathway, providing objective experimental evidence for the treatment of cardiovascular diseases.
高静, 柳洋, 郑曲. 中药刺五加通过cAMP/PKA/PPARγ信号通路抑制AS模型大鼠心肌纤维化的机制研究[J]. 河北医学, 2025, 31(12): 1989-1997.
GAO Jing, LIU Yang, et al. Mechanism Study on the Inhibition of Myocardial Fibrosis in AS Model Rats through cAMP/PKA/PPARγ Signalling Pathway by the Traditional Chinese Medicine Ciwujia. HeBei Med, 2025, 31(12): 1989-1997.
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