川芎嗪对大鼠慢性缺氧性肺动脉高压的保护作用及其与NOS基因表达的关系

以慢性常压缺氧的方法复制了大鼠慢性缺氧性肺动脉高压模型,观察了川芎嗪(LTZ80mg·kg~(-1),iP)对慢性缺氧性肺动脉高压的预防作用及cGMP含量(血浆和肺小动脉)和肺组织一氧化氮合成酶(NOS)基因的mRNA表达之变化.结果表明,慢性缺氧大鼠肺动脉平均压明显升高,但cGMP含量明显降低,肺组织NOS基因mRNA表达明显减弱;cGMP含量与肺动脉平均压呈明显负相关;LTZ对正常大鼠肺动脉压、cGMP含量和肺组织NOS基因的mRNA表达无明显影响,但可使慢性缺氧大鼠上述指标逆转.结果提示慢性缺氧大鼠肺组织NOS基因mRNA表达降低是慢性缺氧性肺动脉高压发病的机制之一,而LTZ增强了慢性缺氧大鼠肺NOS基因mRNA的表达可能是其预防慢性缺氧性肺动脉高压发生的重要机制.

Ligustrazine in the prevention of chronic hypoxic pulmonary hypertension in rat and its relationship to the gene expression of nitric oxide synthase

A model of chronic hypoxic pulmonary hypertension (HPH) was reconstructed in rats exposed to hypoxia with normal pressure for 14 d. Chronic HPH was prevented by giving Ligustrazine (LTZ) in an intraperitoneal dose of 80 mg ?kg-1 wt. twice daily. The mean pulmonary arterial pressure (mPAP), plasma and pulmonary small arterial cGMP level, and mRNA expression of nitric oxide synthase (NOS) gene in lung tissues were studied. The results showed that the mPAP was significantly higher, but plasma and pulmonary small arterial cGMP level as well as mRNA expression of NOS gene in lung tissues were markedly lower in chronic hypoxic rats than those in control animals. LTZcould reverse those changes of above indexes in hypoxic rats, but did not affect those indexes in normal rats. There was a strong negative correlation between cGMP level and mPAP. It is suggested that the lower mRNA expression of NOS gene in hypoxic rats may be one of pathogenetic mechanisms in chronic HPH, and LTZ can increase the mRNA exprssion of NOS gene and the production of nitric oxide in hypoxic rats, which may be an important mechanism in LTZ preventing chronic HPH.