糖蛋白130基因在大鼠梗死心肌中的表达及意义

Significance of expression of GP130 in the infarcted myocardium in rats with acute myocardial infarction

目的 :观察急性心肌梗死 (AMI)后左室梗死区 (LVIZ)糖蛋白 1 3 0 (GP1 3 0 )表达的动态变化与左室重构(LVRM)的关系 ,以及氯沙坦对GP1 3 0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组及氯沙坦组 ,AMI组又依照术后 1 ,3 ,7,1 4,2 1 ,2 8d分为 6组 ,氯沙坦组于术后第 2天起灌胃给药 ,连续 4周。另设假手术组及正常组各 8只为对照。行心脏标本病理分析 ,分别用放射免疫法和氯氨T法测定LVIZ血管紧张素Ⅱ (AngⅡ )和羟脯氨酸(HC)含量 ,用免疫组化法检测LVIZGP1 3 0蛋白水平的表达。结果 :AMI后 ,心脏质量 (HW)、左室质量 (LVW)、左室质量指数 (LVWI)、HC均显著增加 (P <0 .0 5或P <0 .0 1 ) ;AMI组LVIZAngⅡ明显升高 ,与LVRM有相关性 (均P <0 .0 1 ) ;LVIZGP1 3 0蛋白表达在AMI第 1天开始即明显增加 ,7d达高峰 ,以后有所下降 ,但2 8d时仍明显高于假手术组 (P <0 .0 1 ) ;相关分析显示LVIZGP1 3 0蛋白表达与LVIZAngⅡ、LVRM参数间呈正相关(P <0 .0 5或P <0 .0 1 ) ;与AMI2 8d组相比 ,氯沙坦组LVRM明显减轻 ,GP1 3 0蛋白表达明显下调 (P <0 .0 5或P<0 .0 1 )。结论 :大鼠AMI后LVIZGP1 3 0基因的过度表达与LVRM的发生密切相关 ,氯沙坦改善LVRM的机制还可能与抑制GP1 3

Objective:To determine the dynamic changes of expression of GP130 in the infarcted zone of left ventricule (LVIZ) and the relationship between the changes and left ventricular remodeling (LVRM) in rats with AMI, also to evaluate the effect of losartan on GP130 expression. Method: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 different interval at 1, 3, 7,14,21,28 days after MI. Losartan were delivered by direct gastric gavage 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 LVIZ were measured by radioimmunoassay and chloramine T method respectively. The protein level of GP130 in LVIZ was determined by immunohistochemistry analysis. Result:①Heart weight (HW), left ventricular weight(LVW), left ventricular weight index(LVWI) and HC were all significantly increased after MI (P< 0.05 or P< 0.01).②LVIZ AngⅡ was significantly increased after MI and correlated well with LVRM (all P< 0.01).③The protein level of GP130 in LVIZ gradually increased as early as the 1st day after MI, peaked at the 7 th day and declined thereafter, but sustained higher than that in control group at the 28 th day after MI (P< 0.01).④Correlated analysis found that there were significant positive correlations among GP130 protein level,myocardial AngⅡas well as LVRM parameters (P< 0.05 or P< 0.01).⑤GP130 expression was decreased in losartan-treated group with lightened LVRM comparing with the 28th day after MI group (P< 0.05 or P< 0.01). Conclusion:Overexpression of GP130 in LVIZ may play an important role in LVRM after MI, the mechanisms of losartan in preventing LVRM may be partly through depressing GP130 expression.