知母宁对慢性低O2高CO2大鼠肺小动脉结构型和诱导型NOS基因表达的影响

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (10): 1175-1180.

知母宁对慢性低O₂高CO₂大鼠肺小动脉结构型和诱导型NOS基因表达的影响

黄晓颖, 玉良兴, 李明¹, 陈少贤

温州医学院附属第一医院呼吸内科肺心病研究室, 温州 325003, 浙江;
¹深圳三九集团医药研究院, 深圳 518O₂9, 广东

收稿日期:2005-07-14 修回日期:2005-09-01 发布日期:2020-11-23
通讯作者: 黄晓颖,硕士,讲师,主治医师,主要从事肺动脉高压研究。Tel;13819711719 E-mail:zjwzhxy@l26.com
基金资助:
浙江省自然科学基金资助项目(No301484);浙江省教育厅资助项目(NO₂0030719)

Effect of chimonin on expression of inducible-nitric-oxide-synthase andCO₂nstitutive-nitric-oxide-synthase in chronic hypoxic hypercapnic rat pulmonary arterioles

HUANG Xiao-ying¹, WANG Liang-xing¹, LI Ming², CHEN Shao-xian¹

¹Institute of Corpulmonale, Wenzhou Medical College, Wenzhou 325003, Zhejiang China:;
²Institute of Biochemistry, Shenzhen 999 Corporaton Shenzhen 518029, Guangdong, China

Received:2005-07-14 Revised:2005-09-01 Published:2020-11-23

摘要/Abstract

摘要： 目的: 研究知母宁对慢性低O₂ 高CO₂ 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O₂ 高CO₂ 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O₂ 高CO₂ 组m PAP、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O₂ 高CO₂ 组显著低于正常对照组, 知母宁组显著高于低O₂ 高CO₂ 组(p <0.01); (3)低O₂ 高CO₂ 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O₂ 高CO₂组(P<0.01),血浆iNOS活性无明显差异,肺组织匀浆iNOS活性咯高于低O₂ 高CO₂ 组(P<0.05);(4)低O₂ 高CO₂ 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O₂ 高CO₂ 组(P<0.01)。(5)光、电镜下低O₂ 高CO₂ 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O₂ 高CO₂ 大鼠肺小动脉iNOS及cNOS 基因表达,上调NO/NOS体系,使NO合成增多可能为其抑制慢性低O₂高CO₂、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。

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

Abstract: AIM: To study the effect of chmonin onexpression of inducible-nitric-oxide-synthase and CO₂ stitutive-nitric-oxide-synthase in chronic hypoxic hypercapnicrats, and to explore the mechanism of. inhibition on pulmonary hypertension induced by hypoxic hypercapnia.METHODS: Thirty-six Sprague-dawley rats were ran-domly divided into three groups: normal CO₂ group(A), hypoxic hypercapnic group (B), hypoxic hypercapnia chimonin group (C). NO, INOS, CNOS in blood lung homogenate were measured. INOS MRNA and CNOS MRNA was observed in arterioles from rats bthe technique of in situ hybridization. The average valueof integral light density (ID) of INOS MRNA and CNOSMRNA in pulmonary arterioles was detected by an imageanalysor and the relative CO₂ of MRNA and CNOS MRNA was calculated.RESULTS: MPAP was higher in ratsof B group than that of A group and it was much lower inrats of C group than that of B group. Differences of mCAP were not significant in three groups; NO CO₂ncentration inblood serum and lung homogenate in rats of B group were significantly lower than those of A group, and those of Cgroup were significantly higher than those of B group (P< 0.01). The activity of CNOS in blood serum and lunghomogenate in rats of B group were lower than those of Aand C group (P < 0.01). Activity of INOS in blood seand lung homogenate of B group were higher thanof A group (P < 0.01), and there were not signif-cant difference between blood serum INOS in B and Cgroup. C group INOS in lung homogenate were higherthan those of B group (P < 0. 05). Iight microsCO₂py and electron microsCO₂py showed that chimonin reversed the remodeling of pulmonary arterioles induced by hypoxic hypereapnia.CONCLUSION: Chimohin can increase the expression of inducible-nitric-oxide-synthase gene andCO₂nstitutive-nitric-oxide-synthase gene on chronic hypoxichypercapnic rats pulmonary arterioles, and up regulateCNOS/NO system in hypoxic hypercapnic rats may be oneimportant mechanism of the eftect that chimonin inhibithypoxic hypercapnia pulmonary hypertension.

Key words: chimonin, inducible-nitric-oxide-synthase, cnstitutive-nitric-oxide-synthase, anoxia, hypercap-nia, hypertension, pulmonary, gene

中图分类号:

R965

黄晓颖, 玉良兴, 李明, 陈少贤. 知母宁对慢性低O₂高CO₂大鼠肺小动脉结构型和诱导型NOS基因表达的影响[J]. 中国临床药理学与治疗学, 2005, 10(10): 1175-1180.

HUANG Xiao-ying, WANG Liang-xing, LI Ming, CHEN Shao-xian. Effect of chimonin on expression of inducible-nitric-oxide-synthase andCO₂nstitutive-nitric-oxide-synthase in chronic hypoxic hypercapnic rat pulmonary arterioles[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(10): 1175-1180.

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知母宁对慢性低O₂高CO₂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 andCO₂nstitutive-nitric-oxide-synthase in chronic hypoxic hypercapnic rat pulmonary arterioles

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