Maxingxiongting mixture attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the rho-kinase signaling pathway

• 作者: An Xing Li Songtao Weng Xiangwen Wang Xian Wu Hao Zhang Xinyue Gao Jian Yang Renxu Peng Bo
• 来源期刊: 中医杂志（英文版）
• 年，卷（期）: 2020,（6）
• 所属期刊栏目: Research Articles
• 页码范围: 992-998
• 页数: 7页
• 语种: 英文

摘要

OBJECTIVE: To explore the mechanism of Maxingxiongting mixture (MXXTM) on pulmonary hypertension in a rat model established by intraperitoneal injection of monocrotaline solution,smoking and forced swimming.METHODS: A total of 30 male Sprague-Dawley rats were randomly divided into five groups: control group,model group,high-dose of MXXTM group (HM),low-dose of MXXTM group (LM),and fasudil group.The mean pulmonary artery pressure (mPAP) was measured by using a miniature catheter.Lung tissue and right ventricular tissue sections were stained with hematoxylin-eosin.The right ventricle (RV) and left ventricle + septum (LV + S) were weighted.RW(LV + S) was calculated to reflect the degree of right ventricular hypertrophy.Rho/Rho-kinase signaling pathway key proteins (RhoA,ROCK Ⅰ and ROCK Ⅱ) in rat right ventricular tissue were measured by Western blot analysis.The levels of serum hypoxia-inducible factor-1α (HIF-1α),vascular endothelial growth factor (VEGF) and the levels of plasma renin activity (PRA),angiotensin Ⅱ (ANG-Ⅱ),aldosterone (ALD) in rat anticoagulated plasma were all measured by enzyme-linked immunosorbent assay.RESULTS: Compared with the control group,the mPAP and RW(LV+S) in the model group were significantly increased.Administration of fasudil resulted in a significant decrease of mPAP and RW (LV+ S).In the HM group and LM group,mPAP and RV/(LV + S) were significantly lower than the model group.Compared with the control group,the contents of HIF-1α,VEGF,PRA,ANG-Ⅱ and ALD in the model group were significantly increased.The administration of fasudil and high-dose MXXTM significantly reduced the contents of HIF-1α,VEGF,PRA,ANG-Ⅱ and ALD.Compared with the control group,the expression of RhoA,ROCK Ⅰ and ROCK Ⅱ in the right ventricle of the model group were significantly increased.The administration of fasudil and high-dose MXXTM significantly reduced the expression of RhoA and Rock Ⅱ proteins.Our results indicated that high-dose of MXXTM had similar effects on reducing pulmonary artery pressure and improving right ventricular remodeling to fasudil.However,MXXTM was unable to restore parameters above to control levels.CONCLUSIONS: MXXTM attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the Rho-kinase signaling pathway.