Respiration Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Oncology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
J Tradit Chin Med. 2020 Dec;40(6):992-998. doi: 10.19852/j.cnki.jtcm.2020.06.010.
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.
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. RV/(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.
Compared with the control group, the mPAP and RV/(LV+S) in the model group were significantly increased. Administration of fasudil resulted in a significant decrease of mPAP and RV/ (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.
MXXTM attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the Rho-kinase signaling pathway.
探讨麻杏芎葶合剂（MXXTM）对腹腔注射野百合碱溶液、吸烟和强迫游泳建立的大鼠肺动脉高压模型的作用机制。
30 只雄性 Sprague-Dawley 大鼠随机分为 5 组：对照组、模型组、MXXTM 高剂量组（HM）、MXXTM 低剂量组（LM）和法舒地尔组。通过微型导管测量平均肺动脉压（mPAP）。用苏木精-伊红染色肺组织和右心室组织切片。称重右心室（RV）和左心室+室间隔（LV+S）。计算 RV/（LV+S）以反映右心室肥厚程度。用 Western blot 分析大鼠右心室组织中 Rho/Rho-kinase 信号通路关键蛋白（RhoA、ROCK Ⅰ和 ROCK Ⅱ）。酶联免疫吸附试验测定大鼠抗凝血浆中缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）水平和血浆肾素活性（PRA）、血管紧张素Ⅱ（ANG-Ⅱ）、醛固酮（ALD）水平。
与对照组相比，模型组 mPAP 和 RV/（LV+S）明显升高。法舒地尔治疗可显著降低 mPAP 和 RV/（LV+S）。HM 组和 LM 组 mPAP 和 RV/（LV+S）明显低于模型组。与对照组相比，模型组 HIF-1α、VEGF、PRA、ANG-Ⅱ和 ALD 含量明显增加。法舒地尔和高剂量 MXXTM 治疗可显著降低 HIF-1α、VEGF、PRA、ANG-Ⅱ和 ALD 含量。与对照组相比，模型组右心室 RhoA、ROCK Ⅰ和 ROCK Ⅱ表达明显增加。法舒地尔和高剂量 MXXTM 治疗可显著降低 RhoA 和 Rock Ⅱ蛋白表达。结果表明，高剂量 MXXTM 降低肺动脉压和改善右心室重构的作用与法舒地尔相似，但无法使上述参数恢复至对照组水平。
MXXTM 通过抑制 Rho-kinase 信号通路减轻缺氧性肺动脉高压，改善右心室肥厚。
