姜黄素调节基质金属蛋白酶改善大鼠急性肺栓塞的机制研究

Study on the Mechanism of Curcumin Regulating Matrix Metalloproteinase to Improve Acute Pulmonary Embolism in Rats

关键词:  急性肺栓塞  姜黄素  基质金属蛋白酶  肺损伤

Key words:  acute pulmonary embolism  curcumin  matrix metalloproteinases(MMPs)  lung injury

摘要:

目的 探讨姜黄素对急性肺栓塞（acute pulmonary embolism，APE）的治疗效果和对APE大鼠中基质金属蛋白酶（matrix metalloproteinases，MMPs）表达和活性的影响，以期为姜黄素的临床推广提供实验参考依据。方法 SD大鼠随机分为假手术组，APE组，姜黄素低、中、高（50，100，150 mg·kg^-1）剂量组。每组再设置4 h，1 d，3 d 3个时间点，每个时间点6只大鼠，总计90只。采用自体血栓方法，注入血栓栓子至肺动脉诱导APE动物模型。姜黄素处理组于术前2 h以腹腔注射姜黄素。术后各时间点行大鼠肺动脉压（mPAP）、右心室压力（RVP）测定，血气分析。各组大鼠处死后，取血样和肺组织，肺组织行HE染色，对血清ET-1、TXB₂、MMP-2、MMP-9水平和肺组织氧化应激指标进行检测，并采用Western blotting检测MMP-2、MMP-9蛋白表达。结果 诱导建立APE模型后，与假手术组相比，APE大鼠的mPAP、RVP明显升高，动脉PaO₂水平明显降低（P<0.01），并造成肺组织病理学损伤。而与APE组相比，各时间点姜黄素处理组大鼠的mPAP、RVP明显降低，动脉PaO₂水平明显增加，HE染色显示肺组织病理学损伤有一定改善。氧化应激结果显示，姜黄素处理组大鼠肺组织MDA含量降低，SOD活性增加。姜黄素处理组ET-1、TXB₂、MMP-9水平与APE组相比均明显降低，且Western blotting检测MMP-9蛋白表达水平明显降低。结论 姜黄素对APE肺损伤有一定的保护作用，这可能与改善大鼠心肺功能、血气指标和血管内皮功能，减轻肺损伤，减轻氧化应激损伤，调控MMPs的表达水平有关。

Abstract:

OBJECTIVE To explore the therapeutic effect of curcumin on acute pulmonary embolism(APE) and its effect on the expression and activity of matrix metalloproteinases(MMPs) in APE rats, in order to provide experimental reference for clinical popularization of curcumin. METHODS SD rats were randomly divided into sham group, APE group, and curcumin treatment group in low, medium and high doses(50, 100, 150 mg·kg^-1), each group were re-divided into five groups(n=6):4 h, 1 d, and 3 d time point, for a total of 90 rats. After the APE model was established by autothrombotic transfusion into the pulmonary artery, curcumin treatment groups were administrated with curcumin at different dosages 2 h before the surgery. Then rats' mPAP and RVP, blood levels, gas analysis were detected in each group according to the corresponding time point. After anesthetized, blood samples and lung tissues were obtained. Lung tissues was stained by HE staining, serum ET-1, TXB₂, MMP-2, MMP-9 levels, lung tissues MDA content and SOD activity were determined. Western blotting analysis was also used to determine the protein expression of MMP-2 and MMP-9. RESULTS After inducing the APE animal model, the levels of mPAP and RVP were significantly increased, PaO₂ level were significantly decreased compared to those in sham group(P<0.01), significantly histological injury was also observed in lung tissues. Compared with the APE group, the levels of mPAP and RVP were obviously decreased, PaO₂ level were obviously increased in rats of each group treated with curcumin at different time point. HE staining also showed that lung histological injury was also attenuated with curcumin treatment. Oxidative stress results showed that curcumin treatment suppressed the content of MDA and activated the activity of SOD obviously. Serum ET-1, TXB₂, MMP-9 levels were obviously decreased in curcumin treatment groups compared to the APE group. Western blotting results also showed that the protein expression of MMP-9 were obviously suppressed in curcumin treatment groups. CONCLUSION Curcumin has potential protective effect against APE induced lung injury, this might contributed to the improving of lung function, blood gas indicators and vascular endothelial function, attenuating of lung histological injury, oxidative stress, and regulation of MMPs expression.