摘要
目的:探讨G蛋白竞争性抑制性肽(GCIF-27)对野百合碱(monocrotaline,MCT)所诱导的右心室心肌细胞凋亡的影响。方法:SD大鼠随机分为正常组、MCT模型组、GCIP-27低剂量处理组(30μg·kg^-1)和GCIP-27高剂量处理组(90μg·kg^-1)。MCT造模后d1~d21给GCIP-27(ip,bid)干预,d22用右心导管法测右心室收缩压(RVSP);用4%多聚甲醛固定右心室组织,用TdT介导的缺口末端标记法(TUNEL法)检测右心室心肌细胞凋亡情况;免疫组化法检测右心室心肌细胞Bcl-2及Bax抗原表达。结果:与MCT模型组相比,GCIP-27能显著改善MCT所诱导的RVSP的升高(P〈0.05,P〈0.01)、右心室心肌细胞的凋亡(P〈0.01)、Ba。抗原的高表达(P〈0.01)以及Bcl-2抗原的低表达(P〈0.01)。结论:GCIP-27能抑制MCT所诱导的大鼠右心室心肌细胞凋亡,该效应可能与其降低RVSP,上调Bcl-2抗原表达,以及下调Bax抗原的表达相关。
Objective: To determine the effect of C, protein competitive inhibitory peptide (GCIP-27) on the right ventricular eardiomyoeyte apoptosis induced by monocrotaline (MCT) and the possible mechanism. Methods: Sprague-Dawley rats were randomly divided into 4 groups. Cardiomyocyte apoptosis was induced by MCT, and treated with GCIP-27 (30 or 90μg·kg^-1, ip, bid). On day 22, right ventricular systolic pressure (RVSP) was measured through right heart catheterization. The apoptosis of right ventricular cardiomyocytes was detected by TdT mediated nick dUTP end-labeling (TUNEL) technique in the paraffin-embedded right ventrieular tissues. The expression of Bcl-2 and Bax antigens in right ventricular tissues was evaluated by immunohistochemical technique. Results : GCIP-27 significantly inhibited the RVSP (P 〈 0.05 ,P 〈 0.01 ) and reduced the right ventricular eardiomyocyte apoptosis(P 〈 0.01 ). GCIP-27 markedly improved MCT-induced Bax over-expression and Bcl-2 low-expression in right ventricular cardiomyocytes(P 〈 0.01 ). Conclusion: GCIP-27 can attenuate MCT-induced apoptosis of right ventricular cardiomyocytes in rats ; the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax as well as the reduction in RVSP.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2009年第15期1430-1434,共5页
Chinese Journal of New Drugs
基金
国家自然科学基金(30371768,30672641)
重庆市自然科学基金(20048256)
关键词
肽类药物
凋亡
心室重构
野百合碱
polypeptide drug
apoptosis
ventricular remodeling
monocrotaline