主动脉弓狭窄致大鼠慢性心力衰竭模型的建立及病理过程观察

目的观察主动脉弓狭窄致大鼠心力衰竭的病理过程变化。方法沿胸骨剪断大鼠左侧第二根肋骨开胸,于头臂干和左颈总动脉之间行主动脉弓缩窄术(transverse aortic constriction,TAC)建立慢性心力衰竭模型24只,另取大鼠8只行假手术。假手术组于术后12周,模型组分别在TAC术后4周、8周、12周时进行超声心动、血流动力学检测和N端前脑钠素(N-terminal pro-brain natriuretic peptide,NT-pro BNP)测定,并进行心肌组织病理学观察。结果模型组在TAC术后4周时NT-pro BNP显著增加、8周达到峰值(P0.05)、12周时呈下降趋势;超声心动图结果显示,模型组TAC术后4周时射血分数(ejection fraction,EF)、短轴率(fraction shortening,FS)显著升高、左心室收缩末期容积(left ventricular end systolic volume,LVESV)显著减小(P0.05),8周时EF显著升高(P0.05),12周时EF显著降低、左心室舒张末期容积(left ventricular end diastolic volume,LVEDV)、LVESV显著增加(P0.05);血流动力学检测显示,模型组在TAC术后左室最大收缩速率(left ventricular pressure maximal rate of rise,dp/dtmax)降低、左室最大舒张速率(left ventricular pressure maximal rate of fall,﹣dp/dtmax)升高(P0.05);病理学观察显示,模型组TAC术后4周时心肌细胞肥大、排列紊乱,8周时心肌间结缔组织增生、炎症细胞浸润,12周时心肌细胞凋亡、胶原纤维沉积。结论主动脉弓狭窄致大鼠心力衰竭模型在TAC术后4周时心肌出现代偿性肥厚,8周时心肌出现失代偿的初期反应,12周时出现心肌纤维化,形成不可逆的心力衰竭。

Establishment of a rat model of chronic heart failure by transverse aortic constriction and observation of its pathological process

Objective To observe the pathological changes of heart failure caused by transverse aortic constriction in rats. Methods Partial thoracotomy was performed to the second rib and the transverse aortic constriction was performed between the innominate and left carotid arteries to establish a model of heart failure in 24 rats. The same operation was performed on another 8 rats, except for the ligation of the transverse aorta. Echocardiographic assessment, hemodynamic measurement, myocardial histopathological examination and NT-proBNP measurement were performed to the sham group at 12 weeks and model group at 4 weeks, 8 weeks, 12 weeks after the operation. Result At 4 weeks after the operation, NT-proBNP, EF, FS and -dp/dtmax of the model group was significantly increased and LVESV, +dp/dtmax of the model group were significantly decreased (P<0.05). At 8 weeks after the operation, EF and-dp/dtmax of the model group were increased and +dp/dtmax of the model group was significantly decreased (P<0.05). At 12 weeks after the operation, NT-proBNP, EF and +dp/dtmax of the model group were decreased, and LVESV, LVEDV and -dp/dtmax of the model group were increased (P<0.05). The cardiomyocytes became hypertrophic and lined up in disorder at 4 weeks after the operation. Pathologic examination of the myocardial tissue showed connective tissue proliferation and inflammatory cell infiltration at 8 weeks after the operation, and cardiomyocyte apoptosis and collagen fiber deposition at 12 weeks after the operation. Conclusions Transverse aortic constriction induces heart failure in rats. The pathological processes are compensatory hypertrophy at 4 weeks after the operation, initial reaction of decompensation at 8 weeks after the operation, and heart failure at 12 weeks after the operation.