大黄酸通过抑制CDK9/STAT3途径防治低氧性肺动脉高压

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。

Rhein attenuates hypoxia-induced pulmonary hypertension via CDK9/STAT3 pathway

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 cardiac hypertrophy 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.