卡托普利抑制自发性高血压大鼠左心室肥厚机制的研究  

Investigation of the mechanism for inhibition of leftventricular bypertrophy by captopril treatment inspontaneously hypertensive rats

作　　者：陈松苍[1] 陈达光[1] 包幼迪[1] 晋学庆[1] 林应锵[1] 王华军[1] 

机构地区：[1]福建医学院附属第一医院高血压研究室,福建医学院遗传工程研究室

出　　处：《中华医学杂志》1995年第2期74-78,共5页National Medical Journal of China

基　　金：国家自然科学基金

摘　　要：为了探讨血管紧张素转换酶抑制剂阻止左心室肥厚机制，对雄性自发性高血压大鼠（ＳＨＲ）从宫内期起给予卡托普利治疗（治疗ＳＨＲ组，每日１００ｍｇ／ｋｇ），到１６周龄时停药，以年龄、性别配对的ＳＨＲ以及ＷＫＹ大鼠作对照，各组到４０周龄处死。测定血压、左心室重与体重比、心肌羟脯氨酸，去甲肾上腺素含量、左心室ｃ－ｆｏｓ和ｃ－ｍｙｃｍＲＮＡ（Ｎｏｒｔｈｅｒｎｂｌｏｔ）。早期卡托普利治疗显著降低ＳＨＲ血压，停药后，血压仍维持在相对低水平，治疗组的左心室重与体重比及心肌羟脯氨酸含量显著减少，治疗组左心室ｃ－ｍｙｃ表达量与未治疗ＳＨＲ组相比减少７２％，而３组大鼠左心室ｃ－ｆｏｓ表达量和心肌去甲腺上腺素无明显差别。结果显示卡托普利可以阻止高血压形成，持久抑制心肌间质纤维化及心肌肥厚，后者可能是由于抑制心肌ｃ－ｍｙｃ表达的结果，而ｃ－ｆｏｓ表达在心肌肥厚和抑制过程中可能不是必要的。o explore the rnechanisms by which angiotensinconverting enzyme inhibrtor (ACEI) prevents the development of left ventricular hypertrophy (LVH) . capto-pril (Cap 100mg . kg-1 /d was administered orally tomale spontaneously hypertensive rats from intrauterineperiod to 16 weeks of age. Male and agematched un-treated WKY rats and SHR were used as controls. Ex-periments were performed at 40 weeks of age. SBP, leftventricular weight to body weight ratio (LVW/BW) ,myocardial hydroxyproline (Hypro) and norepinephrine(NE) were deterrnined. The levels of c-mvc and c-fosmRNA in the left ventricle were measured bv Northernblot. Early-onset Cap therapy significantly decreasedSBP at 16 weeks of age. After discontinuance of treat-ment for 24 weeks, SBP of SHRcap was still maintainedat a level lower than that of untreated SHR. LVW/BWand Hypro in SHR cap were markedly reduced. The ex-pression of myocardial cmyc mRNA (n= 5) was de-creased by 72% in SHRcap compared with that in theuntreated SHR, but the expression of cfos mRNA(n= 7) and NE was not different between the untreatedSHR, SHRcap and WKY rats. These resuhs indicatethat early Cap treatment may permanently prevent thedevelopment of hypertension, inhibit myocardial hyper-trophy (MH) , and interstitial fibrosis. Furthermore,the prevention of MH is associated with a decrease inmyocardial c-myc mRNA levels, and the developmentand regression of MH may be irrelevant to proto-onco-gene c-fos expression.

关 键 词：心脏扩大 高血压 卡托普利 鼠 药理 

分 类 号：R544.105[医药卫生—心血管疾病] R927.2[医药卫生—内科学]