葛根素对慢性低氧高二氧化碳性肺动脉高压大鼠肺血管低氧诱导因子1α的影响

Effect of puerarin on hypoxia-inducible factor-1 alpha of pulmonary arterioles for rats with chronic hypoxia and hypercapnia-induced pulmonary hypertension

目的：探讨葛根素降低大鼠慢性低氧(O_2)高二氧化碳(CO_2)性肺动脉高压的作用是否与抑制肺小动脉低氧诱导因子1α(HIF-1α)表达有关。方法：清洁级SD雄性大鼠30只随机分为正常对照组(NC)、低O_2高CO_24 wk组(HH)、低O_2高CO_2加葛根素组(HP)。免疫组织化学法检测肺细小动脉HIF-1α蛋白的表达,核酸原位杂交法检测肺细小动脉HIF-1αmRNA表达。结果：HH组平均肺动脉压,右室/(左室+室间隔)重量比高于NC组(P＜0.01),HP组低于HH组(P＜0.01)。HH组血浆一氧化氮含量低于NC组(P＜0.01),HP组高于HH组(P＜0.01)。HH组肺细小动脉HIF-1α蛋白表达及HIF-1αmRNA表达高于NC组(P＜0.01),HP组肺细小动脉HIF-1α蛋白表达及HIF-1αmRNA表达低于HH组(P＜0.05)。结论：葛根素减轻大鼠慢性低O_2高CO_2性肺动脉高压的作用可能与其抑制肺血管HIF-1α表达有关。

AIM： To investigate whether the hypotensive effect of puerarin on the pulmonary pressure of rats chronically exposed to hypoxia-hypercapnia was approached through inhibiting the expression of hypoxia-inducible factor-1 alpha （HIF-1α） in pulmonary arterioles, METHODS： Thirty male Sprague-Dawley rats were randomly divided into three groups： normal control （NC） group, hypoxia-hypercapnia （HH） group and hypoxiahypercapnia with puerarin （HP） group. The expressions of HIF-1α protein and mRNA were detected and recorded from pulmonary arterioles by the techniques of immunohistochemistry and nucleic acid in situ hybridization. RESULTS： Mean pulmonary arterial pressure（mPAP） and the weight ratio of right ventricle（RV） to left ventricle plus septum（LV＋S） were much higher in HH group than those in NC group（P 〈 0.01 ）, and lower in HP group than those in HH group （P 〈 0.01 ）. The content of plasma NO was much lower in HH group than that in NC group（P 〈 0.01 ）, and higher in HP group than that in HH group（P 〈 0.01 ）. Expressions of HIF-1α protein and HIF-1α mRNA in pulmonary arterioles were significantly higher in HH group than those in NC group（P〈 0.01 ）, and lower in HP group than those in HH group（P 〈 0.05）. CONCLUSION： The effect of puerarin on reducing the pulmonary pressure of rats chronically exposed to hypoxia-hypereapnia is probably related to the inhibition of the expression of HIF-1α in pulmonary arterioles.