知母宁对慢性低O_2高CO_2大鼠肺小动脉结构型和诱导型NOS基因表达的影响  

Effect of chimonin on expression of inducible-nitric-oxide-synthase and constitutive-nitric-oxide-synthase in chronic hypoxic hypercapnic rat pulmonary arterioles

作　　者：黄晓颖[1] 王良兴[1] 李明[2] 陈少贤[1] 

机构地区：[1]温州医学院附属第一医院呼吸内科肺心病研究室 [2]深圳三九集团医药研究院

出　　处：《中国临床药理学与治疗学》2005年第10期1175-1180,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省自然科学基金(№301484)浙江省教育厅资助项目(№20030719)

摘　　要：目的：研究知母宁对慢性低O_2高CO_2大鼠肺小动脉结构型一氧化氮合酶(cNOS)和诱导型一氧化氮合酶(iNOS)基因表达的影响，进而了解其对肺动脉高压的防治机制。方法：将SD大鼠分为正常对照组、低O_2高CO_2组、知母宁组。采用图像分析、免疫组化、组织原位杂交、酶动力学等方法，测定各组大鼠动脉血、肺组织NO含量、NOS活性、肺细小动脉iNOS、cNOS及其基因表达的变化。结果：(1)低O_2高CO_2组mPAP、RV／(LV+S)显著高于其他组(P＜0．01)，3组间mCAP比较差异无显著性；(2)血、肺组织匀浆NO含量低O_2高CO_2组显著低于正常对照组，知母宁组显著高于低O_2高CO_2组(P＜0．01)；(3)低O_2高CO_2组血浆及肺组织匀浆cNOS活性显著低于正常对照组(P＜0．01)，iNOS活性均显著高于正常对照组(P＜0．01)；知母宁组大鼠血浆及肺组织匀浆cNOS活性均显著高于低O_2高CO_2组(P＜0．01)，血浆iNOS活性无明显差异，肺组织匀浆iNOS活性略高于低O_2高CO_2组(P＜0．05)；(4)低O_2高CO_2组肺细小动脉iNOS及其mRNA表达显著高于正常对照组(P＜0．01)，cNOS及其mRNA表达显著低于正常对照组(P＜0．01)，知母宁组大鼠肺细小动脉iNOS、cNOS及其mRNA表达均显著高于低O_2高CO_2组(P＜0．01)。(5)光、电镜下低O_2高CO_2组肺血管结构重建，知母宁组肺血管结构重建明显减轻。结论：知母宁能促进低O_2高CO_2大鼠肺小动脉iNOS及cNOS基因表达，上调NO／NOS 体系，使N0合成增多可能为其抑制慢性低O_2高CO_2肺动脉高压和肺血管结构重建的作用的重要作用机制之一。AIM： To study the effect of chmonin on expression of inducible-nitric-oxide-synthase and constitutive-nitric-oxide-synthase in chronic hypoxic hypercapnic rats, and to explore the mechanism of. inhibition on pulmonary hypertension induced by hypoxic hypercapnia. METHODS： Thirty-six Sprague-Dawley rats were randomly divided into three groups： normal control group （A）, hypoxic hypercapnic group （B）, hypoxic hypercapnia ＋ chimonin group （C）. NO, iNOS, cNOS in blood serum and lung homogenate were measured, iNOS mRNA and cNOS mRNA was observed in arterioles from rats by the technique of in situ hybridization. The average value of integral light density （LD） of iNOS mRNA and cNOS mRNA in puhnonary arterioles was detected by an image analysor and the relative content of mRNA and cNOS mRNA was calculated. RESULTS： mPAP was higher in rats of B group than that of A group and it was much lower in rats of C group than that of B group. Differences of mCAPwere not significant in three groups; NO concentration in blood serum and lung homogenate in rats of B group were significantly lower than those of A group, and those of C group were significantly higher than those of B group （ P 〈 0.01 ）. The activity of eNOS in blood serum and lung homogenate in rats of B group were lower than those of A and C group （ P 〈 0.01 ）. Activity of iNOS in blood serum and lung homogenate of B group were higher than those of A group （ P 〈 0.01 ）, and there were not significant difference between blood serum iNOS in B and C group. C group iNOS in lung homogenate were higher than those of B group （ P 〈 0.05）. Light microscopy and electron microscopy showed that chimonin reversed the remodeling of pulmonary arterioles induced by hypoxic hypercapnia. CONCLUSION： Chimonin can increase the expression of inducible-nitric-oxide-synthase gene and constitutive-nitric-oxide-synthase gene on chronic hypoxic hypercapnie rat＇s pulmonary arterioles, and up regulate cNOS/NO system in hypoxic hypercapnic rats ma

关 键 词：知母宁 诱导型一氧化氮合酶 结构型一氧化氮合酶 缺氧 高碳酸血症 肺动脉高压 基因 

分 类 号：R965[医药卫生—药理学]