OBJECTIVE To investigate the protective effect and potential mechanism of Tibetan medicine Ershiwei Chenxiang Wan(ECW) on myocardial fibrosis in rats with hypoxic pulmonary hypertension(HPH).
METHODS Sixty male SD rats were randomly divided into 5 groups: the blank control group, HPH group, HPH+0.6 g·kg−1 ECW group, HPH+1.2 g·kg−1 ECW group, and HPH+trimetazidine(TMZ) group. Except for the blank control group, rats in the other groups were subcutaneously injected with semaxinib(SU5416), and then placed in a hypobaric oxygen chamber for 3 weeks, with the chamber opened for 1 h daily for intragastric administration. The body weight of rats was recorded every day. At the end of the experiment, pulmonary artery pressure(PAP) and right ventricular pressure(RVP) of rats were measured; blood cell count was performed; serum levels of NT-proBNP, CK-MB and LDH were detected by serum biochemical assays; the right ventricular hypertrophy index and heart weight index of rats were calculated; HE staining and Masson staining were used to observe the pathological changes and fibrosis degree of cardiac tissues of rats; Western blotting was applied to determine the protein expressions of Collagen Ⅰ, OPN, Akt, pAkt, GSK-3β, pGSK-3β and β-catenin in rats myocardial tissues.
RESULTS Compared with the blank control group, rats in the HPH group showed slow body weight gain, increased red blood cell count, elevated PAP and RVP, higher serum levels of NT-proBNP, CK-MB and LDH, increased heart weight index and right ventricular hypertrophy index, obvious myocardial fibrosis, up-regulated expression of Collagen Ⅰ, as well as increased expressions of OPN, pAkt, pGSK-3β and β-catenin. After intervention with ECW, all the above abnormal indicators were improved to varying degrees, with more remarkable effects observed in the 1.2 g·kg−1 ECW group.
CONCLUSION Tibetan medicine ECW can effectively alleviate myocardial injury in HPH rats, and its mechanism may be related to inhibiting the activation of OPN/Akt/GSK-3β signaling pathway, down-regulating the expression of pathway-related proteins, thereby reducing the process of myocardial fibrosis.
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