知母宁对慢性低氧高二氧化碳大鼠NO/NOS体系的影响

Effect of chimonin on nitric-oxide-synthase/ nitric-oxide system in chronic hypoxic hypercapnic rats

目的研究知母宁对慢性低氧高二氧化碳性肺动脉高压的防治机制。方法将SD大鼠分为正常对照组,4周低O2高CO2组和4周低O2高CO2+知母宁组(知母宁组)。测定各组大鼠肺动脉平均压(mPAP)、颈动脉平均压(mCAP),检测动脉血、肺组织iNOS、cNOS活性,及NO产生、释放的变化;观察各组大鼠肺细小动脉显微和超微结构的变化。结果①mPAP低O2高CO2组比正常组显著增高,知母宁组比低O2高CO2组显著降低;3组间mCAP比较差异无显著性。②血浆及肺组织匀浆NO含量低O2高CO2组均显著低于对照组,知母宁组均显著高于低O2高CO2组。③血浆及肺组织匀浆iNOS活性低O2高CO2组均显著高于对照组,知母宁组血浆iNOS活性与低O2高CO2组无明显差异,肺组织匀浆iNOS活性略高于低O2高CO2组;血浆及肺组织匀浆cNOS活性低O2高CO2组显著低于对照组,知母宁组均显著高于低O2高CO2组。④光镜电镜下低O2高CO2组,肺细小动脉管壁增厚、管腔变小中膜平滑肌细胞增生、外膜胶原纤维增生,知母宁组肺血管重建减轻。结论知母宁有抑制慢性低氧高二氧化碳性肺动脉高压和肺血管结构重建的作用,上调NO/NOS体系,使NO合成增多可能为其重要作用机制。

OBJECTIVE To study the effect of chmonin on chronic hypoxic hypercapnic pulmonary hypertention and to explore its mechanism. METHODS Thirty-six Sprague-Dawley rats were randomly divided into normal control group （A）, hypoxie hypercapnia group（B） and hypoxie hypercapnia ＋ ehimonin group（C）. Mean pulmonary arterial pressure（mPAP） and mean carotid arterial pressure（reCAP） were measured. NO, tNOS, iNOS, eNOS in blood serum and lung homogenate were measured. RESULTS （ 1 ） mPAP was significantly higher in rats of B group than that of A group and it was much lower in rats of C group than that of hypoxie B group. Differences of reCAP were not significant in three groups; （2）NO concentration in blood serum and lung homogenate in rats of B group were significantly lower than those of A group, those of C group were significantly higher than those of B group. （ 3 ） The activity of eNOS in blood serum and lung homogenate in rats of B group were significantly lower than those of A and C group. Activity of iNOS in blood serum and lung homogenate of B group were significantly higher than those of A group, and there were not significant difference between iNOS in B and C group. （4） Light microscopy and Electron microscopy showed that pulmonary arterioles remodeling in B group,and those remodeling were significantly lower in rats of C group. CONCLUSION Chimonin can inhibit hypoxie hypereapnia pulmonary hypertension and pulmonary vessel remodeling by up regulate eNOS/NO system in hypoxie hypereapnie rats.