Ⅱ型心肾综合征大鼠模型制备方法的改良

Improvement in the establishment method for the type Ⅱ cardio-renal syndrome rat model

目的 建立一种改良的Ⅱ型心肾综合征大鼠模型并进行评估。方法 将20只雄性SD大鼠随机分为假手术组(7只)与模型组(13只)。采用在小动物麻醉机下挤心脏法进行永久性结扎冠状动脉左前降支造成心肌梗死,1周后行单侧肾(右肾)切除术,第6周行心脏超声、病理学染色及血液、尿液等检测来验证模型的建立。结果 与假手术组相比,模型组大鼠心超检测的心功能、内生肌酐清除率明显下降(P<0.01),脑钠肽、血肌酐、尿素氮、24 h尿蛋白明显升高(P<0.01);HE染色发现模型组大鼠心肌排列紊乱,肾小球萎缩伴炎症细胞浸润。苦味酸-天狼猩红染色发现模型组大鼠心肌胶原纤维明显增多,肾小管排列不规则,大量胶原沉积,阳性染色面积比明显升高(P<0.01)。结论 本改良造模方法能够制备一种操作简便、手术创伤小、死亡率低的Ⅱ型心肾综合征大鼠模型,模拟了早期心脏、肾功能损伤和病理改变,为系统深入研究Ⅱ型心肾综合征的发病机制及药效作用机理奠定了基础。

Objective To establish an improved type Ⅱ cardio-renal syndrome rat model and evaluate it.Methods Twenty male SD rats were randomly divided into sham and model groups with 7 rats in the sham group and 13 rats in the model group.The model group received the method of squeezing the heart under a small animal anesthesia machine to permanently ligate the left anterior descending branch of the coronary artery to cause myocardial infarction.One week later,unilateral nephrectomy(right nephrectomy) was performed.The rats underwent cardiac echocardiography,pathological staining,and blood and urine tests at 6 weeks to verify model establishment.Results Compared with the sham group,the cardiac function assessed by echocardiography and the endogenous creatinine clearance rate in the model group rats were significantly decreased(P < 0.01),and the levels of brain natriuretic peptide,blood creatinine,urea nitrogen,and 24 h urine protein in the model group were significantly increased(P < 0.01).HE staining revealed a disordered myocardial arrangement,glomerular atrophy,and inflammatory cell infiltration in model group rats.Picric acid-Sirius red staining showed a significant increase in myocardial collagen fibers,an irregular arrangement of renal tubules,and a large amount of collagen deposition in model group rats.The positive staining area ratio was also significantly increased(P < 0.01).Conclusions This improved modeling method provided a type Ⅱ cardio-renal syndrome rat model with s simple operation,minimal surgical trauma,and low mortality rate.This model simulates the early onset of cardiac and renal function damage and pathological changes in type Ⅱ CRS,laying the foundation for systematic and in-depth research on the pathogenesis and pathological mechanism of type Ⅱ cardio-renal syndrome.