CAJ | 학술논문

目的：糖尿病患者急性心肌梗死（ AMI）后的心室重构及心功能恶化较非糖尿病者更为明显。本研究旨在观察阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能的影响，并探讨其作用是否与肝细胞生长因子及其受体（HGF/c-Met）信号通路有关。方法：70只雄性SD大鼠经链脲霉素（STZ，65 mg/kg）腹腔注射，诱导糖尿病大鼠模型。8周后对糖尿病大鼠结扎左冠状动脉前降支构建AMI大鼠模型，术后存活32只大鼠随机分为2组：AMI对照组（n＝16）和阿托伐他汀干预组（n＝16，阿托伐他汀20 mg· kg-1· d-1），并在糖尿病大鼠中设假手术组（ n＝11），术后24 h予以灌胃给药。2周后比较各组大鼠心功能、心肌组织病理改变、心肌细胞凋亡、HGF和c-Met mRNA及蛋白表达差异。结果：（1） AMI对照组心功能显著低于假手术组（P＜0.05），胶原容积分数、心肌细胞凋亡指数、HGF及c-Met mRNA及蛋白表达均显著高于假手术组（ P＜0.05）；（2）阿托伐他汀干预组的胶原容积分数和心肌细胞凋亡指数显著低于AMI对照组（P＜0.05），心功能、HGF及c-Met mRNA及蛋白表达均显著高于AMI对照组（P＜0.05）。结论：阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能具有显著改善作用；HGF/c-Met信号通路在AMI后会激活，阿托伐他汀的上述作用机制可能与其进一步增强HGF/c-Met信号通路有关。
목적：당뇨병환자급성심기경사（ AMI）후적심실중구급심공능악화교비당뇨병자경위명현。본연구지재관찰아탁벌타정대당뇨병대서AMI후심기세포조망、심실중구급심공능적영향，병탐토기작용시부여간세포생장인자급기수체（HGF/c-Met）신호통로유관。방법：70지웅성SD대서경련뇨매소（STZ，65 mg/kg）복강주사，유도당뇨병대서모형。8주후대당뇨병대서결찰좌관상동맥전강지구건AMI대서모형，술후존활32지대서수궤분위2조：AMI대조조（n＝16）화아탁벌타정간예조（n＝16，아탁벌타정20 mg· kg-1· d-1），병재당뇨병대서중설가수술조（ n＝11），술후24 h여이관위급약。2주후비교각조대서심공능、심기조직병리개변、심기세포조망、HGF화c-Met mRNA급단백표체차이。결과：（1） AMI대조조심공능현저저우가수술조（P＜0.05），효원용적분수、심기세포조망지수、HGF급c-Met mRNA급단백표체균현저고우가수술조（ P＜0.05）；（2）아탁벌타정간예조적효원용적분수화심기세포조망지수현저저우AMI대조조（P＜0.05），심공능、HGF급c-Met mRNA급단백표체균현저고우AMI대조조（P＜0.05）。결론：아탁벌타정대당뇨병대서AMI후심기세포조망、심실중구급심공능구유현저개선작용；HGF/c-Met신호통로재AMI후회격활，아탁벌타정적상술작용궤제가능여기진일보증강HGF/c-Met신호통로유관。
AIM:To investigate the effect of atorvastatin on myocardial apoptosis , ventricular remodeling and cardiac function after acute myocardial infarction (AMI) in diabetic rats, and to explore whether the effect is mediated by hepatocyte growth factor ( HGF)/c-Met signaling pathway .METHODS:Diabetes in 70 male SD rats was induced by in-traperitoneal injection of streptozotocin (STZ, 65 mg/kg).After 8 weeks, AMI was induced by the ligation of the left ante-rior descending coronary artery in the diabetic rats , and 32 surviving rats were divided into AMI group (n=16) and AMI+atorvastatin group ( n=16, 20 mg· kg -1 · d-1 ) at random.The similar surgical procedure was completed in sham group (n=11) without coronary ligation.Atorvastatin was given daily by gavage from the first day after AMI .Two weeks later, the cardiac function , pathological changes of myocardial tissues , myocardial apoptosis , and the expression of HGF and c-Met were compared among groups .RESULTS: AMI significantly reduced cardiac function , increased collagen volume fraction ( CVF) and myocardial apoptotic index , and up-regulated the expression of HGF and c-Met at mRNA and protein levels in AMI control group (P<0.05).The cardiac function was improved , and CVF and myocardial apoptotic index were reduced by the treatment with atorvastatin , which also up-regulated the expression of HGF and c-Met (P<0.05).CON-CLUSION:Atorvastatin significantly attenuates myocardial apoptosis and cardiac remodeling , and improves cardiac func-tion after AMI in diabetic rats by further enhancing the activation of HGF /c-Met pathway .