真武汤对渗透泵恒释ADR肾病综合征大鼠的干预作用

Efficacy of Zhenwu Decoction on Adriamycin-caused Nephritic Syndrome by Osmotic

目的:通过渗透泵恒释技术建立阿霉素肾病综合征(NS)模型,以真武汤干预治疗,评价真武汤对NS大鼠的治疗效果。方法:阿霉素(14.5 mg.kg-1)按渗透泵灌注要求填充,手术植入大鼠腹腔,通过渗透压恒释阿霉素诱发肾病综合征模型,将大鼠随机分为真武汤高、低剂量组(24,12 g.kg-1.d-1),地塞米松组(0.9 mg.kg-1.d-1),给药4周,观察动物一般情况,尿蛋白、血压、血脂、血清蛋白及肾功能指标变化,肾小球IgG表达,评价阿霉素渗透泵肾病综合征模型以及真武汤的干预作用。结果:阿霉素渗透泵NS大鼠成活率显著提高,实验过程中无动物死亡;模型组大鼠第2周出现典型的肾病综合征症状,与空白组比较,24 h尿蛋白、血压、血脂明显升高,血清蛋白及肾功能明显降低(P<0.01);与模型组比较,真武汤高、低剂量组能显著改善NS大鼠精神、活动、摄食量、毛色等状况,明显减轻NS大鼠24 h尿蛋白(109.85±14.65),(49.75±5.14),(51.43±4.46)mg,恢复大鼠血清总蛋白(TP):(57.64±3.64),(61.26±2.21),(60.85±1.91)g.L-1,白蛋白(ALB):(21.70±2.18),(25.93±2.74),(25.00±2.64)g.L-1水平,降低大鼠血清总胆固醇(2.91±0.50),(2.17±0.26),(2.12±0.31)mmol.L-1、甘油三酯(1.05±0.29),(0.49±0.12),(0.61±0.15)mmol.L-1水平,降低大鼠血压、血清尿素氮(BUN)、肌酐(SCr)(P<0.05或P<0.01);减少大鼠肾小球系膜区IgG的沉积。结论:通过渗透泵恒释阿霉素建立肾病综合征模型,可提高造模成功率和模型稳定性,真武汤能减少NS大鼠尿蛋白,提高血浆蛋白水平,减少血液高凝状况,恢复肾功能及肾小球结构,改善NS症状。

Objective： Based on rat adriamycin-caused model of nephritic syndrome （NS） by constant release technology using osmotic pump, to evaluate the efficacy of Zhenwu decoction on NS. Method： Osmotic pump filled with adriamycin （14.5 mg·kg-1） was implanted into rats enterocoelia, then induced the NS on rats by constant release of adriamycin with osmotic pump, and after intervention of Zhenwu decoction, the urine protein, blood pressure, serum lipid parameters, plasmaprotein, renal function indicators, and IgG expression in glomerulus were detected, which was to assess the establishment of model of NS rat and the efficacy of Zhenwu decoction on it. Result： The survival rate of rats with adriamycin-caused NS using osmotic pump was improved significantly, no rats died during experiment.The NS occurred in the rats of model group at second week after giving driamycin, and compared with control group, the urine protein on 24 h and blood pressure were increased significantly after model establishment, and blood lipid, as well as markedly decreased serum protein and renal hypofunction were detected（P〈0.01）. Compared with model group, the mental state, activity, food intake and hair colour of rats were observably improved after administrating lower and higher doses of Zhenwu decoction （24, 12 g·kg-1·d-1）, and both doses were capable of significantly decreasing urine protein and blood pressure（P〈0.01）, recovering rats serum protein level（P〈0.05）, improving blood urea nitrogen（BUN） and serum creatinine（Scr） levels, decreasing the content of total cholesterol（TC） and triglycerides（TG） （P〈0.01）, and the notably decreased IgG deposition in rats mesangial area. Conclusion： The stable model of rat with NS could be successfully established using constant release function of osmotic pump and after intervention with Zhenwu decoction, it showed the efficacy on improving NS from the aspects of decreasing the urine protein, increasing plasma protein level, relieving hypercoagulable state, the decline in contents of BUN and Scr and restoring glomerular structure.