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大黄酸通过抑制CDK9/STAT3途径防治低氧性肺动脉高压
引用本文:陈马云,姚一竹,朱琳,蔡朝阳,徐梓玮,孙君委,王良兴,黄晓颖. 大黄酸通过抑制CDK9/STAT3途径防治低氧性肺动脉高压[J]. 温州医科大学学报, 2022, 52(8): 620-624. DOI: 10.3969/j.issn.2095-9400.2022.08.003
作者姓名:陈马云  姚一竹  朱琳  蔡朝阳  徐梓玮  孙君委  王良兴  黄晓颖
作者单位:温州医科大学附属第一医院 呼吸与危重症医学科,浙江 温州 325015
基金项目:浙江省自然科学基金青年基金项目(LQ19H010003);浙江省医药卫生科技计划项目(2019RC047);温州市基础性科研项目(Y2020250)。
摘    要:目的:探究中药单体大黄酸对低氧性肺动脉高压(HPH)的影响及其作用机制。方法:以SPF级SD大鼠为研究对象,设置常氧组(N)、低氧组(H)、低氧+大黄酸组(HR)。Western blot法检测每组大鼠体内提取的肺组织匀浆中p-CDK9、CDK9、p-STAT3/STAT3、PCNA、Bcl-2、Bax、Caspase-3、Cleaved-Caspase-3(CC-3)蛋白表达差异。以右心导管法插管检测平均肺动脉压(mPAP)评估大鼠的血流动力学情况,称重法检测右心肥厚程度,HE染色后观察血管形态以评估大鼠的肺血管重塑情况。结果:与N组比,H组肺匀浆中p-CDK9、CDK9、p-STAT3/STAT3、PCNA、Bcl-2 蛋白表达均上调,而Bax、Caspase-3、CC-3 蛋白表达下调(均P <0.05),H组大鼠的mPAP及右心肥厚指数显著上升(均P <0.05),管壁面积(WA)/管总面积(TA)明显增加(P <0.05),提示大鼠的肺血管重塑程度明显加重;与H组比,HR组肺匀浆中p-CDK9、CDK9、p-STAT3/STAT3、PCNA、Bcl-2蛋白表达均下调,而Bax、Caspase-3、CC-3 蛋白表达上调(均P <0.05),mPAP及右心肥厚指数显著降低(均P <0.05),WA/TA明显降低(P <0.05),提示肺血管重塑改善。结论:大黄酸可能通过抑制CDK9的表达及磷酸化,抑制STAT3的磷酸化,缓解低氧诱导的大鼠肺动脉高压,改善肺血管重塑和右心肥厚。

关 键 词:低氧性肺动脉高压  大黄酸  细胞周期蛋白依赖性激酶9  信号传导与活化转录因子3  细胞增殖  细胞凋亡  大鼠  
收稿时间:2022-04-12

Rhein attenuates hypoxia-induced pulmonary hypertension via CDK9/STAT3 pathway
CHEN Mayun,YAO Yizhu,ZHU Lin,CAI Chaoyang,XU Ziwei,SUN Junwei,WANG Liangxing,HUANG Xiaoying.. Rhein attenuates hypoxia-induced pulmonary hypertension via CDK9/STAT3 pathway[J]. JOURNAL OF WENZHOU MEDICAL UNIVERSITY, 2022, 52(8): 620-624. DOI: 10.3969/j.issn.2095-9400.2022.08.003
Authors:CHEN Mayun  YAO Yizhu  ZHU Lin  CAI Chaoyang  XU Ziwei  SUN Junwei  WANG Liangxing  HUANG Xiaoying.
Affiliation:Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
Abstract:Objective: To investigate the effect of rhein on hypoxia-induced pulmonary hypertension (HPH) and its mechanism. Methods: Sprague-Daeley (SD) rats were used as the research objects. The SD rats separated into 3 groups: normoxia group (N), hypoxia group (H), hypoxia+rhein group (HR). The expressions of p-CDK9,CDK9, p-STAT3/STAT3, PCNA, Bcl-2, Bax, Caspase-3, CC-3 (Cleaved-Caspase-3) in lung homogenate were revealed by Western blot. The mean pulmonary artery pressure in 3 groups of rat was measured by right heart catheterization method. The degree of right cardiac hypertrophy was measured by weighing, while the degree of pulmonary vascular remodeling in each group of rats was observed by HE staining. Results: Compared with the N group, the p-CDK9, CDK9, p-STAT3/STAT3, PCNA, Bcl-2 protein expression in H group was increased (P<0.05), the Bax, Caspase-3, CC-3 protein expression in H group was reduced (P<0.05), the mPAP, right cardiachypertrophy index and WA/TA in H group were considerably enhanced (P<0.05). In contrast with the H group,the p-CDK9, CDK9, p-STAT3/STAT3, PCNA, Bcl-2 protein expression in HR group was reduced (P<0.05), the Bax, Caspase-3, CC-3 protein expression in HR group was considerably increased (P<0.05), the mPAP, right cardiac hypertrophy index and WA/TA in HR group were reduced (P<0.05). Conclusion: Rhein could inhibit thephosphorylation of STAT3 by inhibiting the expression and phosphorylation of CDK9, thereby alleviating pulmonary hypertension, improving pulmonary vascular remodeling and right heart hypertrophy in HPH rats.
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