不同剂量卡维地洛对急性心肌梗死后心衰大鼠胶原合成的影响

Effect of carvedilol on the production of collagen Ⅰ in Acute Myocardial Infaction Rat

目的探讨卡维地洛对急性心肌梗死模型大鼠梗死区、非梗死区TGF-β1、胶原蛋白分子表达的影响。方法将结扎冠状动脉左前降支40只急性心肌梗死模型鼠随机分成3组:心梗对照组(MI-C)、小剂量卡维地洛治疗组(MI-LC,1mg/kg.d)、大剂量卡维地洛治疗组(MI-HC,10mg/kg.d)。另设假手术组(MI-sham)。同步药物干预8周后,RT-PCR检测梗死区胶原-ⅠmRNA、TGF-β1-mRNA。结果梗死区胶原-I mRNA的表达:与心梗对照组比较,小剂量卡维地洛组、大剂量卡维地洛组表达均下调,差别具显著性(P<0.05);小剂量卡维地洛组与大剂量卡维地洛组表达水平接近,差别无显著性(P>0.05);非梗死区胶原-I mRNA的表达:与心梗对照组比较,小剂量卡维地洛组与大剂量卡维地洛组表达均下调,差别具显著性(P<0.05);小剂量卡维地洛组与大剂量卡维地洛组表达水平接近,差别无显著性(P>0.05)。TGF-β1mRNA的表达如下:与假手术组比较,心梗大鼠的梗死区心肌组织中TGF-β1mRNA的表达上调(P<0.001)。与心梗对照组比较,小剂量卡维地洛组与大剂量卡维地洛组的TGF-β1mRNA表达下调(P<0.01),大剂量卡维地洛组TGF-β1mRNA的水平与小剂量卡维地洛组接近,两组差异没有显著性(P>0.05)。结论卡维地洛能减少梗死区胶原分子的合成,也能减少非梗死区胶原分子的合成,从而延缓整个心肌纤维化的进程,但无剂量依赖关系,其机制可能与抑制TGF-β1的表达有关。

Objective To study the effect of carvedilol on the production of collagen and TGF-β1 in acute myocardial infaction（AMI） rat.Methods Coronary ligation of left anterior descending artery 40 patients with acute myocardial infarction model in rats were randomly divided into three groups：myocardial infarction control group（MI-C）,a small dose of carvedilol treatment group（MI-LC 1 mg/kg.d）,largedose of carvedilol treatment group（MI-HC,10 mg/kg.d）.Separate the sham operation group（MI-the sham）.Eight weeks later,the expressions of collagen types I（collagen I） and TGF-β1 were measured by reverse transcription-polymerase chain reaction（RT-PCR） both in infarct zone（IZ） and non-infarct zone（NIZ）.Results The expressions collagen I IZ were as follow：Compared with sham rats,the expressions of collagen I MI-control rats and the other two admission groups were evidently increased（P0.05）.Compared with MI-control rats,the expressions were down-regulated in MI-LC rats and MI-HC rats.There were no significant differences between MI-LC rats and MI-c HC rats（P0.05）.The expressions collagen I in NIZ were as follow：Compared with sham rats,the expressions of collagen I MI-control rats and the other two admission groups were evidently increased（P0.05）.Compared with MI-control rats,the expressions were down-regulated in MI-metoprolol rats and MI-Carvedilol rats.There were no significant differences between MI-metoprolol rats and MI-carvedilol rats（P0.05）.And also there were no differences between MI-control rats and MI-small rats（P﹥0.05）.TGF-β1 mRNA expression is as follows：compared with the sham group（P0.001） upregulation of TGF-β1 mRNA in the infarcted myocardium of MI rats organization.Control group and AMI in the carvedilol group,small dose of TGF-β1 mRNA is downregulated（P0.01） in the carvedilol group,large doses of TGF-β1 mRNA levels close to the small dose of carvedilol group,two group differences were not significant（P0.05）.Conclusion The Carvedilol reduced the infarct zone collagen molecule synthesis and reducing the synthesis of collagen molecules in non-infarcted area,effectively retard the process of myocardial fibrosis as a whole,but no dose-dependent relationship.