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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 study the preventive and therapeutic effects of ligustrazine (TMP) on chronic hypobaric hypoxic pulmonary hypertension rats and its mechanism. Methods: Male Sprague-Dawley rats were randomly divided into three groups: normal control group, hypobaric hypoxia group and ligustrazine group (100 mg · kg -1 · d -1). To establish a rat model of hypobaric hypoxia pulmonary hypertension and observe the changes of mean pulmonary arterial pressure (mP AP), left carotid artery cannulation mean carotid artery pressure (mC AP), right ventricular hypertrophy index (RVHI) and lung The changes of vascular morphology, the percentage of vascular wall thickness to vessel diameter (WT%) and the percentage of vessel wall area to total vessel area (WA%), and the levels of nitric oxide (NO) ET-1, HIF-1α and VEGF were measured. Results: Compared with the normal control group (P <0.05 or P <0.01), the levels of mP AP, RVHI, WT% and WA% in the TMP group were significantly lower than those in the normal control group Low pressure hypoxia group (P <0.05 or P <0.01). Hypobaric hypoxia had little effect on carotid artery pressure mC AP, but there was no significant difference between the two groups (P> 0.05). The level of NO in serum was significantly lower in hypobaric hypoxia group than in normal control group (P <0.05), and that in ligustrazine group was significantly higher than that in hypobaric hypoxia group (P <0.05). The levels of ET-1, HIF-1α and VEGF in serum were significantly lower in hypobaric hypoxia group than those in normal control group (P <0.05), and those in ligustrazine group were significantly lower than those in hypoxia and hypoxia group (P <0.05). CONCLUSION: TMP can effectively prevent pulmonary hypertension and structural remodeling of pulmonary arterioles induced by hypobaric hypoxia in rats. The mechanism may be related to up-regulation of NO in serum and down-regulation of ET-1, HIF-1α and VEGF.