心功能不全合并糖尿病大鼠模型的建立与评价

Establishment and evaluation of rat model of cardiac insufficiency complicated with diabetes mellitus

目的 制备一种高稳定性心功能不全合并糖尿病大鼠模型,以期方便于临床和实验室研究。方法 取清洁级雄级Wistar大鼠45只,随机分为3组,A组（正常组）10只,B组（腹主动脉缩窄组）10只,C组（腹主动脉缩窄合并糖尿病组）25只。首先对B、C组大鼠采用腹主动脉缩窄的方法构建心功能不全模型,缩窄2个月后,将C组大鼠随机分为5个亚组,C1~5,分别采用单次腹腔注射40、45、50、55、60 mg/kg链脲佐菌素（STZ）的方法诱导心功能不全合并糖尿病大鼠模型。实验过程中动态观察大鼠一般状况及体质量改变,监测STZ注射后72 h、4周大鼠血糖水平,并于STZ注射后1个月对各组大鼠进行心脏超声及心肌病理改变评价。结果 对比不同剂量,STZ为45 mg/kg时,构建模型稳定性高且成模大鼠一般状况、血糖水平、心脏超声、心肌组织镜下形态学较正常组发生明显变化,符合心功能不全合并糖尿病改变。结论 采用腹主动脉缩窄2个月后腹腔单次注射45 mg/kg STZ的方法诱导心功能不全合并糖尿病动物模型,方法简便可靠,稳定性高。

Objective To establish a rat model of cardiac insufficiency complicated with diabetes mellitus （DM）, and to meet the needs of clinical and laboratory studies. Methods Forty-five male specific pathogen free （SPF） rats were randomly divided into three groups： normal control group （A, n=10 ）, coarctation of the aorta （AAC） group （B, n=10）, AAC＋DM group （C, n=25）. The model of cardiac insufficiency with abdominal aortic constriction was establish in B and C groups. After two months of AAC, rats of group C were randomly divided into five subgroups and treated with different doses of streptozotoein （STZ） respectively（40, 45, 50, 55 and 60 mg/kg）. The dynamic changes of general condition and weights were observed during the process of experiment. The blood glucose levels of 72 h and 4 week after STZ injection were detected. The echocardiograph and cardiac pathology changes were evaluated after 1 month of STZ injection. Results The general data ineluding blood glucose levels, echocardiographic findings and myocardial tissue microscopic morphology were compared be-tween different doses of STZ groups. The 45 mg/kg STZ was considered for more stable model of cardiac dysfunction compli- cated with diabetes mellitus. Conclusion The rat model of cardiac insufficiency complicated with diabetes meUitus is estab- lished by single dose injection of 45 mg/kg STZ after two-month AAC, which is a simple, reliable and high stability method.