贝那普利对自发性高血压大鼠心肌纤维化及心肌肿瘤坏死因子表达影响  

Effect of benazepril on myocardial fibrosis and the expression of tumor necrosis factor-α in spontaneously hypertensive rats

作　　者：孙绍贤[1,2] 李海涛[1] 刁增利[1] 赵红[1] 王蔓莉[1] 

机构地区：[1]华北煤炭医学院附属医院心内科,河北唐山063000 [2]秦皇岛市妇幼保健院内科,河北秦皇岛066000

出　　处：《现代医学》2010年第1期1-6,共6页Modern Medical Journal

基　　金：河北省教育厅资助项目(No.2004120);河北省卫生厅资助项目(No.04263);华北煤炭医学院附属医院学院级课题(No.08009)

摘　　要：目的:研究贝那普利在预防自发性高血压大鼠(SHR)心肌纤维化中的作用及对心肌肿瘤坏死因子-α(TNF-α)表达的影响。方法:16只6周龄SHR分为实验组(SHR-con组)和药物干预组(SHR-ben组),7只同周龄WKY鼠为正常血压对照组(WKY组)。SHR-ben组给予贝那普利(10 mg.kg-1.d-1)灌胃12周,其余两组蒸馏水灌胃,均每日1次。颈动脉插管,测颈动脉收缩压(SBP)和舒张压(DBP),天狼猩红染色,计算机图像分析软件分析心肌切片的胶原容积分数(CVF)和心肌小动脉周围胶原面积与小动脉管腔面积比(PVCA/LA);偏振光显微镜观察Ⅰ、Ⅲ型胶原(像素表示),计算Ⅰ/Ⅲ型胶原之值,观察心肌纤维化程度;用冰冻切片(免疫组化法)观察心肌TNF-α表达。结果:喂养12周后与WKY组比,SHR-con组SBP和DBP明显升高,CVF、PVCA/LA、Ⅰ/Ⅲ胶原之值亦显著升高(P<0.01),TNF-α表达亦增多;而SHR-ben组各指标较SHR-con组均显著性下降(P<0.01),贝那普利有效降低SHR的SBP、DBP,亦使CVF、PVCA/LA、Ⅰ/Ⅲ胶原之值均明显下降,改善SHR左心室纤维化,且下调TNF-α表达。结论:长期应用贝那普利治疗可预防和部分逆转高血压大鼠心肌纤维化,其机制可能与贝那普利除能降低血压外,还能降低心肌局部TNF-α表达有关。Objective： To study the effect of benazepril on myocardial fibrosis and the expression of tumor necrosis factor-α（TNF-α） in spontaneously hypertensive rats（SHR）. Methods： Sixteen SHRs were randomly divided into two groups ： experiment group （ SHR- con group） and medical intervenning group （ SHR- ben group）. Seven WKYs were as the normal hypertension controls（WKY group）. SHR-con group were fed benazepril （ 10 mg-kg-1 -d-1 ） for 12 weeks. The others groups were received distilled water. Systolic blood pressure（SBP） and diastolic blood pressure（DBP） were detected by a tube that was plugged into the carotid artery and were connected with electronicphysiological polyconductor machine. Picrosirius red staining combined with computed myocardial fibrosis were employed to evaluate the collagen volume fraction （CVF）, perivasular collagen area/luminal area ratio （PVCA / LA） and immunohistochemical staining evaluated TN-α on ice s/ice expression in the left ventricular size tissue. Results： Compared with WKY group, the SBP, DBP, CVF, PCVA/LA and TNF-α expression （ P 〈 O. O1 ） increased markedly in SHR-con group, while these targets had decreased in SHR-ben group compared with SHR- con group. Conclusion： Chronic administration of benazepril inhibits and regresses the development of myocardial fibrosis in SHR. Except for the decreasing the blood pressure, TNF-（~ may be involved in the reversal mechanism of myocardial fibrosis by benazepril.

关 键 词：贝那普利 自发性高血压 心肌纤维化 肿瘤坏死因子-α 大鼠 

分 类 号：R542.23[医药卫生—心血管疾病] R544.1[医药卫生—内科学]