姜黄素通过NLRP3/Caspase-1/IL-1β轴对低氧性肺动脉高压的干预作用

doi:10.3969/j.issn.2095-9400.2020.02.003

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摘要目的：探讨姜黄素对低氧性肺动脉高压（HPH）的作用及其机制。方法：同时研究肺动脉平滑肌细胞（PASMCs）和SD大鼠肺组织，PASMCs和SD大鼠都设置为常氧组（N）、低氧组（H）、低氧+姜黄素组（HC）3组。CCK-8法测3组PASMCs细胞活力，Western blot法检测3组PASMCs和肺匀浆中NLRP3、Caspase-1及IL-1β蛋白表达差异。血流动力学检测3组大鼠的平均肺动脉压（mPAP）及右心肥大程度，HE染色观察3组大鼠肺血管重塑程度。结果：与N组比，H组PASMCs的数量有明显增加（P＜0.05），H组PASMCs和肺匀浆中NLRP3、Caspase-1、IL-1β蛋白表达均上升（均P＜0.05），H组大鼠的mPAP及右心肥大指数明显升高（均P＜0.05），发生明显肺血管重塑；与H组比，HC组PASMCs的数量明显降低（P＜0.05），PASMCs和肺匀浆中NLRP3、Cas-pase-1、IL-1β蛋白表达均下降（均P＜0.05），HC组大鼠的mPAP及右心肥大指数明显降低（均P＜0.05），肺血管重塑改善。结论：姜黄素可能通过抑制NLRP3/Caspase-1/IL-1β轴，改善低氧PASMCs异常增殖、HPH大鼠肺血管重塑和右心肥大，降低肺动脉压力。

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关键词 ：低氧性肺动脉高压, Nod样受体蛋白3, Caspase-1, IL-1&beta, 姜黄素, 大鼠

Abstract：Objective: To investigate the therapeutic effect and mechanism of curcumin in hypoxia-induced pulmonary hypertension (HPH). Methods: Pulmonary artery smooth muscle cells (PASMCs) and Sprague-Daeley (SD) rats were studied in vitro and in vivo respectively. The PASMCs and SD rats were divided into 3 groups: normoxia group (N), hypoxia group (H), hypoxia+curcumin group (HC). The activity of PASMCs cells in each group was measured by cck-8, and the expressions of NLRP3, Caspase-1 and il-1β protein in PASMCs were detected by Western blot. The average pulmonary artery pressure and the degree of right cardiac hypertrophy in each group of rats were measured by hemodynamics, while the degree of pulmonary vascular remodeling in each group of rats was observed by HE staining, and the expression difference of the above-mentioned proteins in the lung homogenate in each group of rats was detected by western blot. Results: Compared with the N group, the quantity of PASMCs in H group were significantly increased. The NLRP3/Caspase-1/IL-1β protein expression in H group was increased. The mPAP and right cardiac hypertrophy index in group H were significantly increased, and the pulmonary vascular remodeling was obvious. Compared with the H group, the quantity of PASMCs in HC group were significantly decreased, and the expression of NLRP3/Caspase-1/IL-1β protein in PASMCs and lung homogenate was decreased, mPAP and right cardiac hypertrophy index were significantly decreased in HC group, and pulmonary vascular remodeling was improved. Conclusion: Curcumin could inhibits pulmonary arterial hypertension, pulmonary vascular remodeling and right ventricle hypertrophy via suppressing NLRP3/Caspase-1/IL-1β axis mediated inflammatory reaction.

Key words： hypoxic pulmonary arterial Nod-like receptor protein 3 Caspase-1 IL-1β curcumin rats

基金资助:浙江省自然科学基金资助项目（LQ19H010003）；浙江省医药卫生科技项目（2019RC047，2019RC208）；温州市科技计划项目（Y20180601，Y20160219）。

通讯作者: 黄晓颖，主任医师，教授，Email：zjwzhxy@126.com。

作者简介: 蔡学定（1981-），男，浙江温州人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2020.02.003 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I2/98

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