心肌营养素-1在心肌梗死后大鼠重塑心肌中的表达及意义

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目的:研究急性心肌梗死(AMI)后左室非梗死区(LVNIZ)心肌营养素 1(CT 1)表达的动态变化与左室重塑(LVRM)的关系以及氯沙坦对 CT 1 表达的影响。方法:56 只雄性 Wistar大鼠 AMI术后 24h随机分为:AMI组及氯沙坦组,AMI组又依照术后1、3、7、14、21、28 d 6 个不同时间点分为 6 组。氯沙坦组于术后第 2天起灌胃给药 20 mg·kg-1 ·d-1,连续 4 周,另设假手术组及正常组为对照,各 8 只。采用放射免疫法测定LVNIZ血管紧张素Ⅱ(AngⅡ)含量,氯氨T法测LVNIZ胶原含量(HC),用RT PCR法检测LVNIZ CT 1mRNA表达。结果:①与正常及假手术组相比,AMI组 LVNIZ AngⅡ、HC明显升高 (P<0.05~0.01),与 LVRM相关性好(P<0.01);②LVNIZ- CT 1mRNA表达于AMI 1d即开始升高,且进行性增加,14 d达高峰,以后有所下降,28 d时仍明显高于假手术组(P<0.05~0.01);③相关分析显示 CT -1mRNA表达水平与心肌 AngⅡ、HC、LVRM 正相关(P<0.05~0.01);④与AMI 28 d组相比,氯沙坦组 LVRM明显减轻,LVNIZ AngⅡ、HC 明显下降,CT 1mRNA表达下调(P<0.05)。结论:大鼠AMI后 LVNIZ CT- 1 基因的过度表达与 LVRM发生密切相关,氯沙坦改善LVRM的机制还可能是通过影响CT 1转录实现,值得进一步研究。 Objective: To investigate the relationship between the dynamic changes of left ventricular non-infarcted area (LVNIZ) and cardiac troponin 1 (LVRM) after acute myocardial infarction (AMI) and the effect of losartan on CT 1 expression. Methods: Fifty-six male Wistar rats were randomly divided into AMI group and losartan group at 24 hours after operation. The AMI group was divided into 6 groups according to the time points of 1,3,7,14,21,28 d group. The losartan group was administrated with 20 mg · kg -1 · d -1 intragastrically on the second day after the operation for 4 weeks. Another 8 rabbits in the sham operation group and the normal group were used as control. LVNIZ angiotensin Ⅱ (AngⅡ) content was measured by radioimmunoassay, LVNIZ collagen content (HC) was measured by chloramine T method, and LVNIZ CT 1 mRNA expression was detected by RT PCR. Results: ①Compared with normal and sham-operated group, the LVNIZ AngⅡ, HC in AMI group were significantly increased (P <0.05-0.01), and LVRM was significantly correlated with LVRM (P <0.01); ②The expression of LVNIZ- CT 1 mRNA began at 1 day after AMI (P <0.05 ~ 0.01) .③The correlation analysis showed that the expression level of CT-1 mRNA correlated with the levels of AngⅡ, HC , LVRM (P <0.05-0.01) .④Compared with AMI 28 d, the LVRM of losartan group was significantly reduced, and the levels of LVNIZ AngⅡ, HC and CT 1 mRNA were significantly decreased (P <0.05). CONCLUSION: The overexpression of LVNIZ CT-1 gene after AMI is closely related to the occurrence of LVRM. The mechanism of losartan in improving LVRM may be achieved by affecting CT 1 transcription, which is worth further study.
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