Lin Xiangang, Chen Yenong, Liu Zhuqing
Acupuncture Clinical Traumatology Institute, Anhui University of Chinese Medicine, Hefei 230031, China.
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.
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.
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。