大鼠急性心肌梗死后gp130基因异常表达的意义及氯沙坦干预的影响

Significance of abnormal expression of gp130 gene in rats after AMI and the effect of losartan on gp130

目的 研究急性心肌梗死 (AMI)后左室非梗死区 (LVNIZ)糖蛋白 130 (glucoprotein130 ,gp130 )表达的动态变化与左室重塑 (LVRM )的关系以及氯沙坦 (losartan)对 gp130表达的影响。方法 AMI术后 2 4h存活的 73只雄性Wistar大鼠随机分为 :AMI组及losartan组 ;AMI组又依照术后 1、3、7、14、2 1、2 8d 6个时间点分为六组 ,另设 8只假手术 (Sham )鼠及 8只正常鼠为对照组。losartan组于术后第二天起灌胃给药 (2 0mg·kg-1·d-1) ,连续 4周。行心脏标本病理分析 ,分别用放免法和氯氨T法测定LVNIZ的AngⅡ和羟脯氨酸含量 ,分别用RT PCR和Western blot法检测LVNIZgp130mRNA及蛋白水平的表达。最终获完整资料大鼠于上述各组分别为 9、8、8、9、9、8、9、8和 8只。结果 (1)与正常对照组及Sham组相比 ,AMI组心脏重量 (HW )、左室重量 (LVW )、左室重量指数 (LVWI)、心肌细胞横径 (TDM)、羟脯氨酸含量均显著增加 (P <0 0 5～ 0 0 0 1) ;(2 )AMI组LVNIZ的AngⅡ明显升高 ,与LVRM相关性好 (P <0 0 1～ 0 0 0 1) ;(3)LVNIZgp130mRNA及蛋白表达于心肌梗死 (MI)第 1天即开始明显增加 ,7d达高峰 ,以后有所下降 ,但 2 8d时仍明显高于对照组 (P <0 0 5～ 0 0 0 1) ;(4)

Objective To study the dynamic changes of expression of gp130 both at mRNA and protein level in non-infarction zone of left ventricule (LVNIZ) and the relationship between those changes and left ventricular remodeling (LVRM) in rats with AMI, also to evaluate the effect of losartan on gp130 expression. Methods The 73 surviving AMI male Wistar rats were randomly divided into 2 groups at 24 hours after MI: AMI group and losartan treatment group, the former was subdivided into 6 groups according to the different interval at 1, 3, 7,14,21,28 days after MI. Losartan were delivered by direct gastric gavage (20 mg·kg -1 ·d -1 ) for 4 weeks beginning at the 2nd day after AMI. Sham-operated and normal rats were selected randomly to serve as non-infarcted controls. LVRM was evaluated by pathologic analysis, AngⅡand hydroproline concentration (HC) in LVNIZ were measured by radioimmunoassay and chloramine T method respectively. The mRNA and protein level of gp130 in LVNIZ were determined by RT-PCR and Western-blot analysis respectively. Complete experimental data were obtained in rats being 9, 8, 8, 9, 9, 8, 9, 8and 8 respectively in each group mentioned above. Results (1) Compared with sham-operated rats and control rats, heart weight (HW), left ventricular weight(LVW), left ventricular weight index(LVWI), TDM, HC in the 28 th day after MI group were all significantly increased ( P <0.05～0.001).(2) LVNIZ AngⅡwere significantly increased after MI and correlated well with LVRM ( P <0.01～0.001).(3)The mRNA and protein level of gp130 in LVNIZ gradually increased as early as the 1st day after MI, peaked at the 7 th day and declined thereafter, but sustained higher than those in sham-operated rats at the 28 th day after MI ( P <0.05～0.001).(4) Correlated analysis found that there were significant positive correlation among gp130 mRNA and protein level,myocardial AngⅡas well as LVRM parameters ( P <0.05～0.001). (5) Myocardial AngⅡ and gp130 expression at mRNA and protein were all decreased in losartan-treated group with lightened LVRM as compared with the 28th day after MI group( P <0.05～0.01). Conclusion Overexpression of gp130 in LVNIZ may play an important role in LVRM after MI, the mechanisms of losartan in preventing LVRM may be partly through depressing gp130 expression, which is worth to study further.