5/6肾切除联合ISO制备心肾综合征大鼠模型方法初探

Preliminary study on the method of preparing cardiorenal syndrome rat model by 5/6 nephrectomy combined with ISO

关键词:  5/6肾切除  异丙肾上腺素  大鼠  心肾综合征  模型

Key words:  5/6 nephrectomy  isoproterenol  rat  cardiorenal syndrome  model

摘要:

[目的] 查阅已有的心肾综合征大鼠模型文献报道，将"5/6肾切除术制备心肾综合征大鼠模型"方法适当改进，评价其方案造模效果，探讨简捷高效的心肾综合征造模方法。[方法] 将20只雄性SD大鼠随机分为两组，即空白组与手术组，空白组大鼠不做处理，手术组大鼠均按"两次手术法"行5/6肾切除，手术1周后连续2 d（间隔24 h）皮下注射异丙肾上腺素（2.5、1.5 mg/kg）制备心肾综合征模型。分别检测两组大鼠造模后的血肌酐（Cr）、血尿素氮（BUN）、脑钠肽（BNP）水平，比较造模前、造模后、造模6周大鼠体质量，并在造模6周后处杀两组大鼠，称取心脏质量，计算心脏质量指数（心脏质量/大鼠体质量），观察两组大鼠心、肾病理组织变化。[结果] 大鼠经5/6肾切除联合异丙肾皮下注射方法造模后，空白组与手术组BNP、Cr水平差异有统计学意义（P<0.05），手术组大鼠活动后喘息明显、耳廓苍白、被毛稀疏干枯且生长缓慢，体质量较空白组明显降低（P<0.05），心、肾组织病理均较空白组有明显改变。[结论] 5/6肾切除联合ISO皮下注射制备心肾综合征大鼠模型方法有效，是一种简捷高效的心肾综合征造模方法，可以为心肾综合征动物实验提供模型基础。但该法由于不完全模拟慢性肾功能衰竭导致心力衰竭的自然病程，可能不适用于研究该病早期发展变化规律，而对于心肾综合征的药物治疗评价及机制研究较为合适。

Abstract:

[Objective] Referring to the existing literature on rat models of cardiorenal syndrome,we preparing rat model of cardiorenal syndrome by 5/6 nephrectomy. [Methods] Twenty male SD rats were randomly divided into two groups,the blank group and the operation group. The rats in the blank group were not treated. All rats in the operation group underwent 5/6 nephrectomy according to "two operations". After one week of operation,isoprenaline (2.5 mg/kg,1.5 mg/kg) was injected subcutaneously for two consecutive days (24 h interval) to establish the model of cardiorenal syndrome. The levels of serum creatinine (Cr),serum urea nitrogen (BUN) and brain natriuretic peptide (BNP) were measured in the two groups. The body mass of rats before,after and 6 weeks after model establishment was compared. Six weeks after the establishment of the model,the rats of the two groups were killed,and the heart mass was weighed,and the heart mass index (heart mass/rat body mass) was calculated. The pathological changes of heart and kidney were observed. [Results] After 5/6 nephrectomy combined with subcutaneous injection of isoproterenol in rats,there were significant differences in BNP and Cr levels between the blank group and the operation group (P<0.05). The rats in the operation group had obvious asthma after exercise. For example,the auricle is pale,the coat is sparse and dry and grows slowly. Compared with the blank group,the body weight of the two groups was significantly lower (P<0.05). The pathological changes of heart and kidney were significant differences. [Conclusion] 5/6 nephrectomy combined with ISO subcutaneous injection is a simple and efficient method for the establishment of rat models of cardiorenal syndrome. It can provide a new way for us to further explore the mechanism of the occurrence and drug treatment. However,this method does not fully simulate the natural course of heart failure caused by chronic renal failure. It may not be suitable for studying the early development of the disease,but it is more suitable for evaluating the drug treatment and disease mechanism of cardiorenal syndrome.