摘要
目的:研究川芎嗪(TMP)对慢性低压低氧性肺动脉高压模型大鼠的防治作用及其机制。方法:将雄性SD大鼠随机分为3组,即正常对照组、低压低氧组与川芎嗪组(100 mg·kg^(-1)·d^(-1))。建立低压低氧性肺动脉高压大鼠模型,观察TMP干预后大鼠平均肺动脉压力(mP AP)、左颈总动脉插管测平均颈动脉压(mC AP)、右心室肥厚指数(RVHI)和肺血管形态学的改变,计算肺细小动脉管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%),以及大鼠血清中一氧化氮(NO)、内皮素-1(ET-1)、缺氧诱导因子-1α(HIF-1α)与血管内皮生长因子(VEGF)水平。结果:检测TMP干预21 d,大鼠mP AP、RVHI、WT%和WA%各指标比较,低压低氧组显著高于正常对照组(P<0.05或P<0.01),川芎嗪组显著低于低压低氧组(P<0.05或P<0.01)。低压低氧条件对颈动脉压力mC AP影响不大,组间比较差异均无统计学意义(P>0.05)。血清中NO含量比较,低压低氧组显著低于正常对照组(P<0.05),川芎嗪组显著高于低压低氧组(P<0.05)。血清中ET-1、HIF-1α与VEGF含量比较,低压低氧组显著高于正常对照组(P<0.05),川芎嗪组显著低于低压低氧组(P<0.05)。结论:TMP可有效预防大鼠低压低氧导致的肺动脉高压和肺小动脉的结构重建,其作用机制可能与上调大鼠血清NO含量和下调ET-1、HIF-1α与VEGF活性有关。
Objective: To investigate the preventive effect of tetramethylpyrazine (TMP) on hypoxic pulmonary hypertension in rats and the underlying mechanism. Methods: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: the normal control group, hypobaric and hypoxic group and TMP group ( 100 mg ·kg^-1 ·d^-1 ). After the animal models of hypobaric and hypoxic pulmonary hypertension were established, mean pulmonary artery pressure ( mPAP), mean carotid artery pressure ( mCAP), ratio of right ventricular/(lift ventricular + interventricular septum) (RVHI) and morphological changes of pulmonary vessels were observed and the rates of wall thickness/external diameter ( WT% ) and wall area/total vascular area (WA%) were calculated. The contents of nitric oxide ( NO), endothelin-1 ( ET-1 ), hypoxic-inducible factor-1 ( HIF-1 ) and vascular endothelial growth factor (VEGF) were detected in serum after the 21-day treatment with TMP. Results: The values of mPAP, RVHI, WT% and WA% of hypobaric and hypoxic group were significant higher than those of the normal control group ( P 〈 0.05 or P 〈 0.01 ), and those of TMP group were obviously lower than those of hypobaric and hypoxic group (P 〈 0.05 or P 〈 0.01 ). The condition of hypobaric and hypoxic had no significant effect on mCAP, and there were no significant differences among the groups (P 〉 0.05). The values of NO in serum of hypobaric and hypoxic group was lower than those of the normal control group (P 〈 0.05) and those of TMP group were obviously higher than those of hypobaric and hypoxie group (P 〈 0.05 ). The values of ET-1, HIF-1α and VEGF in serum of hypobarie and hypoxic group were higher than those of the normal control group ( P 〈 0.05 ) and those of TMP group were obviously lower than those of hypobaric and hypoxie group ( P 〈 0.05 ). Conclusion: TMP can effectively prevent pulmonary hypertension induced by hypobaric and hypoxic and structural remodeling of pulmonary arterioles. The mechanism may be related to the content up-regulation of NO and activity down-regulation of ET-1, HIF-1α and VEGF in serum of rats.
出处
《中国药师》
CAS
2017年第4期607-611,共5页
China Pharmacist
基金
陕西省科技攻关社发基金项目(编号:2014K11-01-01-01)
关键词
川芎嗪
低压低氧
肺动脉高压
一氧化氮
内皮素-1
缺氧诱导因子-1
血管内皮生长因子
Tetramethylpyrazinei Hypobaric and hypoxic
Pulmonary hypertension
Nitric oxide
Endothelin-1
Hypoxic-inducible factor-1
Vascular endothelial growth factor