阿司匹林改善缺血性心脏病小鼠模型的心肌纤维化

Aspirin attenuates myocardial fibrosis in mice with ischemic heart disease

目的探讨阿司匹林对左前降支动脉结扎术诱导的缺血性心脏病小鼠心肌纤维化的作用。方法选用C57BL/6小鼠24只,均行左前降支结扎术。术后第4周,采用随机数表法将小鼠分为对照组和阿司匹林组,每组12只;阿司匹林组小鼠每日予20 mg/kg阿司匹林灌胃,对照组小鼠予等剂量0.9%氯化钠溶液灌胃,均干预4周。术后第4周(干预前)和第8周(干预后),经超声心动图检查记录心功能指标(左室射血分数、左室舒张末内径),采用Masson染色评估心肌纤维化程度(心肌瘢痕相对长度、心肌纤维化比例)。术后第8周,采用Western blot检测小鼠心肌组织中环氧合酶1(Cox-1)、α-平滑肌肌动蛋白(α-SMA)、α1-Ⅰ型胶原(Col1α1)蛋白质相对表达量。结果术后第4周,两组间小鼠的左室射血分数和左室舒张末内径的差异均无统计学意义(P值均>0.05);术后第8周,阿司匹林组小鼠左室射血分数显著高于对照组(P=0.0015),左室舒张末内径显著低于对照组(P=0.0001)。Masson染色结果显示,术后第4周,两组间小鼠心肌瘢痕长度和纤维化比例的差异均无统计学意义(P值均>0.05);术后第8周,阿司匹林组小鼠心肌瘢痕长度和纤维化比例均显著低于对照组(P值均<0.01)。术后第8周,阿司匹林组小鼠心肌组织中Cox-1、α-SMA、Col1α1的蛋白质表达量均显著低于对照组(P值均<0.05)。结论阿司匹林可改善缺血性心脏病小鼠模型的心功能障碍及心肌纤维化。

Objective To investigate the effect of aspirin on the myocardial fibrosis in mice with ischemic heart disease induced by left anterior descending ligation.Methods A total of 24 C57BL/6 mice underwent left anterior descending ligation.At 4 weeks after surgery,the mice were randomly divided into control group and aspirin group,with 12 mice in each group.Intragastric administration of aspirin(20 mg/kg)and normal saline were given daily for 4 weeks in the aspirin group and control group,respectively.Cardiac function(left ventricular ejection fraction[LVEF]and left ventricular end-diastolic diameter[LVEDd])and fibrosis(relative scar length and proportion of fibrosis)were assessed by echocardiography and Masson staining at 4 and 8 weeks postoperatively.Western blot was used to detect the protein levels of cyclooxygenase 1(Cox-1),α-smooth muscle actin(α-SMA)andα1-collagenⅠ(Col1α1)in myocardial tissues at 8 weeks after surgery.Results There was no significant difference in the LVEF or LVEDd at 4 weeks after surgery between the two groups(both P>0.05).At 8 weeks after surgery,a higher level of LVEF(P=0.0015)and a lower level of LVEDd(P=0.0001)were reported.There was no significant difference in the relative scar length or proportion of fibrosis at 4 weeks after surgery between the two groups(both P>0.05).At 8 weeks after surgery,smaller scar length and lower proportion of fibrosis were also reported(both P<0.01).Meanwhile,the protein expression levels of COX-1,α-SMA and Col1α1 in myocardial tissues treated with aspirin were significantly decreased(all P<0.05).Conclusion Aspirin can improve cardiac function and attenuate fibrosis in mice with ischemic heart disease.