姜黄素对慢性阻塞性肺疾病大鼠肺动脉平滑肌细胞的作用及其机制研究

Effect and its molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease

目的：探讨姜黄素对慢性阻塞性肺疾病（COPD）模型大鼠肺动脉平滑肌细胞的作用及其分子生物学机制。方法：将75只雄性Wistar大鼠随机分为正常对照组，模型对照组，姜黄素小剂量组、中剂量组和大剂量组，采用HE染色法观察肺动脉管组织学形态，免疫组织化学染色检测增殖细胞核抗原（PCNA）、凋亡相关蛋白Bcl-2、Bax，TUNEL法检测姜黄素对平滑肌细胞凋亡的影响，蛋白质印迹法检测肺组织SOCS-3／JAK2／STAT通路相关蛋白表达情况。结果：模型对照组右心室收缩压（RVSP）、右心室肥大指数（RVMI）均高于正常对照组（均P〈0．05），姜黄素大剂量组和中剂量组RVSP、RVMI均低于模型对照组（均P〈0．05）；模型对照组肺动脉管增厚、平滑肌细胞数量显著增多，而姜黄素中剂量组和大剂量组肺动脉管变薄、平滑肌细胞固缩、变形；模型对照组PCNA、Bcl-2相对表达量高于正常对照组（均P〈0．05），Bax相对表达量低于正常对照组（P〈0．05）；姜黄素中剂量组和大剂量组PCNA相对表达量低于模型对照组（均P〈0．05），Bax相对表达量高于模型对照组（均P〈0．05）；模型对照组SOCS-3蛋白减少、而磷酸化JAK2、STAT1、STA13增多，姜黄素中剂量组和大剂量纽SOCS．3蛋白增多，磷酸化JAK2、RVMISTAT3减少。结论：姜黄素可促进COPD大鼠平滑肌细胞凋亡，改善平均肺动脉压以及RVMI，这一作用可能与刺激SOCS-3／JAK2／STAT信号途径有关。

Objective： To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease （COPD）. Methods： A total of 75 male Wistar rats were randomly divided into control group （group CN）, model group （group M）, low-dose curcumin group （group CL）, medium-dose curcumin group （group CM） and high-dose curcumin group （group CH ）. HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen （PCNA）, apoptosisrelated protein Bcl-2 and Bax were detected by immunohistochemical staining. TUNEL kit was used to analyze the effects of curcumin on apoptosis of smooth muscle cells, and the protein expressions of SOCS-3/JAK2/STAT pathway in lung tissues were determined by western blot. Results： Right ventricular systolic pressure （RVSP） and right ventricular hypertrophy index （RVMI） in group M were significantly higher than those in group CN, group CH and group CM （ all P 〈 0. 05 ）. HE staining and TUNEL kit test showed that the number of pulmonary artery smooth muscle cells had a significant increase in group M, while the pulmonary artery tube became thin, and the smooth muscle cells shrinked in group CM and group CH. Immunohistochemistry showed that PCNA and Bcl-2 in group M were significantly higher than those in group CN （ all P 〈 0. 05）, while Bax expression was significantly lower than that in group CN （P 〈 0. 05 ）. PCNA in group CM and group CH were significantly lower than that in group M （ all P 〈 0. 05）, while Bax expression was significantly higher than that in group M （P 〈 0. 05 ）. Western blot showed that SOCS-3 protein was significantly decreased in group M, while the p-JAK2, p-STAT1, p-STAT3 were significantly increased （ all P 〈 0. 05）. Compared with group M, SOCS-3 protein in group CM and group CH were significantly increased （ all P 〈 0. 05 ）, while the p-JAK2, p-STAT3 were significantly reduced （ all P 〈 0. 05 ）. Conclusion： Curcumin could promote the apoptosis of smooth muscle cells in rats with COPD, and improve the mean pulmonary artery pressure and RVM[ through stimulating SOCS-3/JAK2/STAT signaling pathway.