| 王贞丽,姜萍,李丙华,等.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[J].中国海洋药物,2022,41(4):51-58. |
| 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 |
| 投稿时间：2022-07-13 修订日期：2022-07-21 |
| DOI： |
| 中文关键词: 芍药苷 肺动脉高压 肺血管重塑 氧化应激 |
| English Keywords:peoniflorin pulmonary arterial hypertension pulmonary vascular remodeling oxidative stress |
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| 中文摘要: |
| 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 60只SD大鼠随机分为6组，每组10只，分别为：对照组（等体积生理盐水，ig）、模型组（等体积生理盐水，ig）、阳性对照组（西地那非25 mg/kg，ig）、芍药苷低、中、高剂量组（20、40、80 mg/kg，ig）。对照组大鼠置于正常环境中饲养，其余各组均于给药0.5 h后置于全自动低压低氧舱内（大气压50 kPa，氧浓度10%），每天8 h，持续21 d。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、GSH-Px活性、降低MDA含量，减轻大鼠肺组织氧化应激损伤有关。 |
| English Summary: |
| Objective To study the effect of (peoniflorin, PF) on hypoxic pulmonary hypertension in rats and to explore its mechanism. Methods A total number of 60 SD rats were randomly divided into 6 groups with 10 rats in each group: Control (normal saline, ig), hypoxic model (normal saline, ig), positive control (sildenafil 25 mg/kg, ig), PF low, middle and high-dose groups (20, 40, 80 mg/kg, ig). The rats in the control group were fed in normal environment, and the other groups were placed in automatic low-oxygen chamber (50 kPa, O2 10%) for 8 h with the duration of consecutive 21 days. 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), HE staining showed that the wall thickening and lumen narrowing of pulmonary arterioles were alleviated after administration of PF. Conclusion PF can reduce the degree of hypoxia pulmonary hypertension and right ventricular hypertrophy in rats, and alleviate the pulmonary arterioles remodeling. The mechanism may 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. |
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