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姜黄素对慢性阻塞性肺疾病大鼠模型肺动脉平滑肌细胞的作用及其分子机制

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

作者信息

Lin Xiangang, Chen Yenong, Liu Zhuqing

机构信息

Acupuncture Clinical Traumatology Institute, Anhui University of Chinese Medicine, Hefei 230031, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016 May 25;45(5):469-476. doi: 10.3785/j.issn.1008-9292.2016.09.04.

Abstract

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). 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), apoptosis-related 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. 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 <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 <0.05), while Bax expression was significantly lower than that in group CN (<0.05). PCNA in group CM and group CH were significantly lower than that in group M (all <0.05), while Bax expression was significantly higher than that in group M (<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 <0.05). Compared with group M, SOCS-3 protein in group CM and group CH were significantly increased (all <0.05), while the p-JAK2, p-STAT3 were significantly reduced (all <0.05). Curcumin could promote the apoptosis of smooth muscle cells in rats with COPD, and improve the mean pulmonary artery pressure and RVMI through stimulating SOCS-3/JAK2/STAT signaling pathway.

摘要

探讨姜黄素对慢性阻塞性肺疾病(COPD)大鼠模型肺动脉平滑肌细胞的影响及其潜在分子机制。将75只雄性Wistar大鼠随机分为对照组(CN组)、模型组(M组)、低剂量姜黄素组(CL组)、中剂量姜黄素组(CM组)和高剂量姜黄素组(CH组)。采用苏木精-伊红(HE)染色观察肺动脉形态。通过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和Bax。使用TUNEL试剂盒分析姜黄素对平滑肌细胞凋亡的影响,采用蛋白质印迹法检测肺组织中SOCS-3/JAK2/STAT通路的蛋白表达。M组的右心室收缩压(RVSP)和右心室肥厚指数(RVMI)显著高于CN组、CH组和CM组(均P<0.05)。HE染色和TUNEL试剂盒检测显示,M组肺动脉平滑肌细胞数量显著增加,而CM组和CH组肺动脉管径变细,平滑肌细胞萎缩。免疫组织化学显示,M组PCNA和Bcl-2显著高于CN组(均P<0.05),而Bax表达显著低于CN组(P<0.05)。CM组和CH组PCNA显著低于M组(均P<0.05),而Bax表达显著高于M组(P<0.05)。蛋白质印迹法显示,M组SOCS-3蛋白显著降低,而p-JAK2、p-STAT-1、p-STAT3显著升高(均P<0.05)。与M组相比,CM组和CH组SOCS-3蛋白显著增加(均P<0.05),而p-JAK2、p-STAT3显著降低(均P<0.05)。姜黄素可促进COPD大鼠平滑肌细胞凋亡,并通过刺激SOCS-3/JAK2/STAT信号通路改善平均肺动脉压和RVMI。

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