[Junren Bufei Yixin颗粒通过PTBP1/PKM2信号通路减轻低氧性肺高血压]
Run-Xiu Zheng1, Shi-Zhong Wang2, Jun-Lan Tan3
1School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine Changsha 410208, China Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine Changsha 410208, China.
概括
俊仁Bufei Yixin颗粒 (JRBF) 通过向聚皮里米丁通道结合蛋白1 (PTBP1) /酸激酶M2型异酶 (PKM2) 途径,有效治疗缺氧性肺高血压 (HPH). 这种治疗降低了肺动脉压力和血管重塑,提供了一种新的治疗方法.
科学领域:
- 心血管研究研究心血管研究
- 肺部医学 肺部医学
- 药理学 药理学是指药理学的学科.
背景情况:
- 缺氧性肺高血压 (hypoxic pulmonary hypertension,HPH) 是一种严重的疾病,其特征是由于缺氧导致肺动脉压力升高.
- 聚胺管结合蛋白1 (PTBP1) /酸激酶异酶M2型 (PKM2) 信号通路在HPH的发病过程中起着至关重要的作用.
研究的目的:
- 为了研究Junren Bufei Yixin颗粒 (JRBF) 对HPH的治疗作用.
- 阐明涉及PTBP1/PKM2信号通路的潜在治疗机制.
主要方法:
- 建立了HPH的小鼠模型,并用不同剂量的JRBF或西尔代纳菲尔治疗.
- 评估了右心室缩压 (RVSP),心声学参数和组织病理学变化.
- 西方斑点和免疫光试验被用来分析PTBP1,PKM2和PKM1的表达和同局部.
- 在体外研究中使用人类肺动脉光滑肌细胞 (hPASMCs) 来评估JRBF对增殖,迁移和代谢途径的影响.
主要成果:
- JRBF显著降低了RVSP,改善了心声学指数 (PAAT/PET比率,TAPSE),并减弱了肺动脉动脉重塑和心肌纤维化.
- 治疗JRBF抑制了PTBP1和PKM2的表达,导致肺组织和hPASMCs中的乳酸积累减少.
- 在体外,JRBF抑制了hPASMC的增殖和迁移,同时降低了PTBP1/PKM2的表达和乳酸盐的产生.
结论:
- 在缓解HPH进展方面,JRBF表现出显著的治疗效果.
- 该机制涉及抑制PTBP1/PKM2轴和恢复糖溶性流量.
- JRBF代表了一种有前途的HPH治疗药物.
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