764-3对野百合碱性肺动脉高压大鼠肺动脉胶原沉积的影响  

Effect of 7643 on Collagen Deposition in the Wall of Pulmonary Artery in Pulmonary Hypertensive Rats Induced by Monocrotaline

作　　者：柳志红[1,2] 程显声[1,2] 蔡如升 孙本韬 朱宜明[1,2] 李亚辉 李炳太 李群[1,2] 

机构地区：[1]中国医学科学院中国协和医科大学 [2]山西医学院

出　　处：《中国循环杂志》1998年第1期50-52,共3页Chinese Circulation Journal

基　　金：国家自然科学基金

摘　　要：目的：观察７６４－３对野百合碱（ＭＣＴ）性肺动脉高压大鼠肺动脉胶原沉积的影响，探讨其可能的作用机制。方法：将雄性Ｗｉｓｔａｒ大鼠随机分为４组即正常组，正常给药组，ＭＣＴ对照组，ＭＣＴ给药组。给药大鼠从第１５天起，皮下注射７６４－３（４０ｍｇ／ｋｇ）１次／日。实验结束时，行血流动力学和病理形态学检查，并测定肺动脉羟脯氨酸（ＨＹＰ）和总蛋白含量。结果：ＭＣＴ性肺动脉高压大鼠肺动脉羟脯氨酸含量较正常组明显增高，平均分别为２４９．５±４９．９μｇ和１２４．２±２１．７μｇ（Ｐ＜０．００１），泡内肺肌型动脉中膜平滑肌细胞（ＳＭＣ）肥大、呈分泌型改变，细胞间胶原沉积；７６４－３能显著降低肺动脉羟脯氨酸含量（平均由２４９．５±４９．９μｇ降至１８６．８±３８．５μｇ，Ｐ＜０．０１），中膜ＳＭＣ结构逆转，胞体多细长，细胞间胶原减少。结论：７６４－３能部分抑制胶原在肺动脉壁的过度沉积，降低ＭＣＴ性肺动脉高压。而其减少胶原沉积、降低肺动脉高压的机制。? Objective:To investigate the effect of 7643 on collagen deposition in the wall of hypertensive pulmonary arteries(PA) in rats treated with monocrotaline (MCT) and the possible mechanism. Methods:Wistar rats were randomly divided into 4 groups:group 1(n=8),normal control without any treatment;group 2(n=8),after feeding for 15 days,rats treated with subcutaneous injection of 7643 (40 mg/kg) once daily for 2 weeks;group 3(n=10),intraperitonel administration of MCT 60 mg/kg at the beginning of experiment to establish pulmonary hypertension but without therapy;and group 4(n=10),the pulmonary hypertension induced as group 3 and treated with 7643 as group 2.At the end of test,the hemodynamics,pathological morphology and biochemical parameters were measured.  Results:Hydroxyproline (HYP) content of PA in MCTtreated rats increased from 1242±217 μg to 2495±499 μg(p<0001).The smooth muscle cells(SMCs) in the media of muscular intraacinar PA showed hypertrophy with a change in phenotype,and a striking increase in collagen production;7643 could reduce HYP content of PA(from 2495±499 μg to 1868±385 μg,p<001).Most of SMCs in the media became thin and long with a reversion of phenotype,and the collagen deposition decreased. Conclusions:7643 can partially prevent excess deposition of collagen in PA and attenuate MCTinduced pulmonary hypertension.Its mechanism is most likely to be the change of SMCs phenotype in hypertensive pulmonary vasculatures.

关 键 词：肺动脉高压 野百合碱 764-3 肺动脉 胶原沉积 

分 类 号：R543.205[医药卫生—心血管疾病]