Pulmonary artery hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, which was with limited therapeutic options. It has been proved that cannabidiol (CBD) had antioxidant effects in many cardiovascular diseases, whereas the efficacy of CBD in PAH is unknown. To defined the effect of CBD in PAH, we explored the functions of CBD in both PASMCs proliferation test in vitro, and preventive and therapeutic PAH rodent models in vivo. The roles of CBD in mitochondria function and the oxidant stress were assessed in human PASMCs and PAH mice. We found that CBD significantly inhibited hyperproliferation of hypoxia-induced PASMCs, and intragastrically administered CBD could reverse the pathological changes in both Sugen-hypoxia and MCT- induced PAH mice models. Mechanical analysis demonstrated that CBD alleviated PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, inhibiting abnormal glycolysis and lactate accumulation in cannabinoids receptors-independent manner. Thus, CBD could be a potential drug for PAH.

中文翻译：

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卡那比二醇通过正常化血管平滑肌细胞中的线粒体功能来减轻肺动脉高压

肺动脉高压（PAH）是一种与肺动脉平滑肌细胞（PASMC）增殖增强和线粒体功能障碍有关的慢性疾病，治疗选择有限。已经证明，大麻二酚（CBD）在许多心血管疾病中具有抗氧化作用，而CBD在PAH中的功效尚不清楚。为了定义CBD在PAH中的作用，我们探索了CBD在体外PASMC增殖测试以及体内预防和治疗PAH啮齿动物模型中的功能。在人PASMC和PAH小鼠中评估了CBD在线粒体功能和氧化应激中的作用。我们发现CBD显着抑制了缺氧诱导的PASMCs过度增殖，胃内施用的CBD可以逆转Sugen-hypoxia和MCT诱导的PAH小鼠模型的病理变化。力学分析表明，CBD通过恢复线粒体能量代谢，使缺氧诱导的氧化应激正常化，抑制异常糖酵解和以大麻素受体非依赖性方式抑制乳酸积累来减轻PAH。因此，CBD可能是PAH的潜在药物。