芍药苷对大鼠低氧性肺动脉高压的防治作用及其抗氧化机制研究  

Protective effect of paeoniflorin on rats with hypoxic pulmonary hypertension by suppressing oxidative stress

作　　者：王贞丽 姜萍 李丙华[2] 季滨龙 WANG Zhen-li;JIANG Ping;LI Bing-hua;JI Bin-long(Department of Quality Management Section,Qingdao Special Service Sanatorium Center of PLA Navy,Qingdao 266071,China;Department of Pharmacy,Qingdao Eighth People's Hospital,Qingdao 266100,China;Department of Emergency,Hospital 971 of The Navy of Chinese PLA,Qingdao 266071,China)

机构地区：[1]海军青岛特勤疗养中心质量管理科,山东青岛266071 [2]青岛市第八人民医院药学部,山东青岛266100 [3]海军第九七一医院急诊科,山东青岛266071

出　　处：《中国海洋药物》2022年第4期51-58,共8页Chinese Journal of Marine Drugs

基　　金：青岛市科技局项目(17-3-3-32-nsh)资助。

摘　　要：目的 研究芍药苷对低氧诱导的肺动脉高压大鼠模型的作用并初步探讨其作用机制。方法 设置对照组、模型组、阳性对照组、芍药苷低、中、高剂量组,在实验终点时检测各组大鼠平均肺动脉压(mPAP)、平均颈动脉压(mCAP)、右心室肥厚指数(RVHI)及观察肺动脉病理变化;检测血浆内皮素(ET-1)、血清一氧化氮(NO)水平;检测肺组织匀浆超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量。结果 与对照组比较,模型组大鼠mPAP、RVHI、血浆ET-1水平、肺组织中MDA含量显著升高(P<0.01),血清中NO水平、肺组织中SOD、CAT、GSH-Px活性显著降低(P<0.01),HE染色显示大鼠肺小动脉管壁明显增厚,管腔狭窄。与模型组比较,芍药苷中、高剂量组大鼠mPAP、RVHI、血浆ET-1水平、肺组织中MDA含量显著降低(P<0.05或P<0.01),血清中NO水平、肺组织中SOD、CAT、GSH-Px活性显著升高(P<0.05或P<0.01);HE染色显示不同剂量芍药苷干预后,大鼠肺小动脉管壁增厚和管腔狭窄均不同程度减轻。结论 芍药苷可降低低氧诱导的大鼠肺动脉高压与右心室肥厚程度,减轻肺小动脉血管重塑,其机制可能与降低大鼠血浆ET-1水平、升高血清NO水平,改善血管内皮舒缩因子失衡,提高大鼠肺组织匀浆中SOD、CAT、GSHPx活性、降低MDA含量,减轻大鼠肺组织氧化应激损伤有关。Objective To study the effect of peoniflorin(PF) on hypoxic pulmonary hypertension in rats and to explore its mechanism. Methods Control, hypoxic model, positive control, PF low, middle and highdose groups were set. Mean pulmonary artery pressure(mPAP), mean carotid artery pressure(mCAP), right ventricular hypertrophy index(RVHI) and pulmonary artery pathological changes were observed at the end of the experiment. Plasma Endothelin-1(ET-1) and serum Nitric oxide(NO) levels were detected. Superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-PX) activity and malondialdehyde(MDA)content of lung tissue homogenate were detected. Results Compared with the control group, the levels of mPAP, RVHI, ET-1 and MDA content in hypoxic model group were significantly increased(P<0.01), while the levels of NO, SOD, CAT and GSH-Px were significantly decreased(P<0.01). HE staining showed significant thickening of pulmonary arteriole wall and narrowing of lumen in rats. Compared with model group, the levels of mPAP, RVHI, ET-1 and MDA of PF middle and high dose groups were significantly decreased(P<0.05 or P<0.01), and the levels of NO, SOD, CAT and GSH-Px were significantly increased(P<0.05 or P<0.01), and HE staining showed that the wall thickening and lumen narrowing of pulmonary arterioles were alleviated after administration of PF. Conclusion PF could reduce the degree of hypoxia pulmonary hypertension and right ventricular hypertrophy in rats, and alleviate the pulmonary arterioles remodeling. The mechanism might be related to reducing plasma ET-1 level, increasing serum NO level, improving the imbalance of vascular endothelial vasomotor factor, increasing the activities of SOD, CAT and GSH-Px, reducing MDA content in lung tissue homogenate, and alleviating oxidative stress injury of lung tissue in rats.

关 键 词：芍药苷 肺动脉高压 肺血管重塑 氧化应激 

分 类 号：R285[医药卫生—中药学]