川芎嗪对野百合碱诱导大鼠肺动脉高压的影响及机制

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Effects and mechanism of tetramethylpyrazine on monocrotaline induced pulmonary arterial hypertension in rats

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doi:10.6040/j.issn.1671-7554.0.2022.0107

Abstract: Objective To investigate the effects and mechanism of tetramethylpyrazine(TMP)on monocrotaline(MCT)induced pulmonary arterial hypertension(PAH)in rats. Methods A total of 36 male SD rats were randomly divided into control, model and TMP groups, with 12 rats in each group. The rats in the model and TMP groups were given intraperitoneal injection of MCT 50 mg/kg on the 1st day to establish PAH model. After 28 days, the TMP group was given tetramethylpyrazine 80 mg/kg by gavage once a day for 4 weeks. At the end of the experiment, the right ventricular systolic pressure(RVSP)was detected and right ventricular hypertrophy index(RVHI)was counted; the pathomorphological changes of lung tissue were observed with hematoxylin-eosin(HE)staining and Masson staining, and the percentage of wall thickness(WT%)and wall area(WA%)were calculated. The structure of lung tissue was observed with a transmission electron microscope. The expressions of Hippo signal pathway related proteins YAP1, WWTR1 and TEAD1 in lung tissue were detected with immunohistochemical staining and Western blotting. Results Compared with the control group, the model group had increased RVSP and RVHI(P<0.001, P<0.001), significantly narrowed lumen of pulmonary arteries, proliferated collagen fibers, and increased protein expressions of YAP1, WWTR1 and TEAD1(P=0.004, P<0.001, P=0.013). Compared with the model group, the TMP group had decreased RVSP and RVHI(P=0.001, P<0.001), improved pulmonary artery remodeling and right ventricular hypertrophy, reduced fibrosis, and decreased protein expressions of YAP1, WWTR1 and TEAD1(P=0.045, P=0.011, P=0.034). Compared with the control group, the TMP group had increased RVSP and RVHI(P=0.045, P=0.045), and increased protein expressions of YAP1, WWTR1 and TEAD1(P=0.080, P=0.013, P=0.468), in which, the difference of WWTR1 protein expression was significant, suggesting that TMP has limited effects. Conclusion TMP has effects on MCT-induced PAH rat model. The underlying mechanism may be related to the inhibition of expressions of Hippo signal pathway related proteins.

Key words: Tetramethylpyrazine, Pulmonary arterial hypertension, Hippo signaling pathway, Pulmonary vascular remodeling, Yes-associated protein 1

CLC Number:

R544

ZENG Yuanyuan, YANG Dongpeng, DONG Zhu, ZHANG Ben, CAO Yiqiu, WANG Xiaowu. Effects and mechanism of tetramethylpyrazine on monocrotaline induced pulmonary arterial hypertension in rats[J].Journal of Shandong University (Health Sciences), 2022, 60(11): 63-69.

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