知母宁对慢性低氧高二氧化碳大鼠肺小动脉胶原代谢的影响  

The effect of chimonin on collagen metabolism of pulmonary arterioles in chronic hypoxic rats

作　　者：黄晓颖[1] 徐晓梅[1] 钱国清[1] 王良兴[1] 

机构地区：[1]温州医学院附属一医呼吸内科,浙江温州325003

出　　处：《中国应用生理学杂志》2010年第2期217-221,共5页Chinese Journal of Applied Physiology

基　　金：浙江省自然科学基金资助项目(M303617);浙江省教育厅资助项目(20030719)

摘　　要：目的:研究知母宁对慢性低O2高CO2大鼠肺小动脉Ⅰ、Ⅲ型胶原代谢的影响,并探讨其可能机制。方法:将SD大鼠36只随机分为正常对照组,4周低O2高CO2组,4周低O2高CO2+知母宁组。采用图像分析、氯胺T法、免疫组化、组织原位杂交技术等方法,监测各组大鼠肺动脉平均压(mPAP)、颈动脉平均压(mCAP)、肺细小动脉显微和超微结构、血CO浓度,血清及肺组织血红素氧合酶-1(HO-1)活性,肺组织羟脯氨酸含量,肺小动脉Ⅰ、Ⅲ型胶原及其基因表达的变化。结果:低O2高CO2组mPAP升高,肺细小动脉管壁增厚,管腔变小,中膜平滑肌细胞和外膜胶原纤维增生,肺血管重建形成,肺匀浆羟脯氨酸含量升高,肺小动脉Ⅰ型胶原及其mRNA表达增加;知母宁组上述变化均明显减轻(P均<0.01)。此外,低O2高CO2组全血CO含量、血浆及肺组织匀浆HO-1活性升高,知母宁组上述指标较低O2高CO2组进一步升高(P均<0.01)。三组间mCAP,Ⅲ型胶原及其mRNA表达无显著差异(P>0.05)。结论:知母宁降低慢性低O2高CO2性肺动脉高压,减轻肺血管结构重建与其抑制肺动脉Ⅰ型胶原增殖有关,上调内源性CO/HO体系的表达为其可能重要机制。Objective：To study the effect and mechanism of chimonin on pulmonary arteriolesⅠand Ⅲ type collagen metabolism in pulmonary hypertension rats induced by chronic 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）.Collagen Ⅰ,Ⅲ and their mRNA,Blood CO concentration（COHb%）,activity of HO-1 in blood serum and lung homogenate,content of hydroxyproline in lung homogenate,pulmonary arteriole micromorphometric index were observed.Results：Hypoxic hypercapnic rats’s mPAP,Hyr of lung homogenate,content of Ⅰtype collagen andⅠtype collagen mRNA in pulmonary arterioles,were significantly higher than those in control group,pulmonary vessel remodeling of hypoxic hypercapnic rats was significant,those changes in hypercapnia＋chimonin group were significantly lower than those in hypoxic hypercapnic group.Blood CO concentration,activity of HO-1 in blood serum and lung homogenate in rats of hypoxic hypercapnic rats were significantly higher than those of control group,and those of hypercapnia＋chimonin group were even higher than hypoxic hypercapnic group （P0.01）.There was no significant difference in mCAP,content of Ⅲ type collagen and their mRNA in three groups（P0.05）.Conclusion：Chimonin can reduce pulmonary hypertension and pulmonary vessel remodeling induced by hypoxic hypercapnia through inhibiting proliferation of collagenⅠ,the mechanism maybe is up regulating endogenous carbon monoxide system.

关 键 词：知母宁 胶原 缺氧 高碳酸血症 肺动脉高压 一氧化碳 血红素氧合酶 

分 类 号：R332[医药卫生—人体生理学]