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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: To establish adriamycin nephrotic syndrome (NS) model by osmotic pump constant-release technique and use Zhenwu Tang intervention to evaluate the therapeutic effect of Zhenwu Decoction on NS rats. METHODS: Adriamycin (14.5 mg.kg-1) was infused into the peritoneal cavity of rats according to osmotic pump perfusion. The model of nephrotic syndrome induced by doxorubicin was established by osmotic pressure. The rats were randomly divided into Zhenwu Tango , Low dose group (24,12 g.kg-1.d-1) and dexamethasone group (0.9 mg.kg-1.d-1) for 4 weeks. The general condition, urinary protein, blood pressure , Blood lipids, serum proteins and renal function indicators, glomerular IgG expression, evaluation of adriamycin-infiltrating pump nephrotic syndrome model and Zhenwu Tang’s intervention. Results: The survival rate of adriamycin-infiltrating NS was significantly increased and no animals died during the experiment. The typical symptoms of nephrotic syndrome were observed in the second week in model group. Compared with the blank group, 24 h urinary protein, blood pressure, (P <0.01). Compared with the model group, the Zhenwu decoction high and low dose groups can significantly improve the state of spirit, activity, food intake, coat color and other conditions in NS rats, significantly reduce the NS The serum total protein (TP) of rats (57.64 ± 3.64), (61.26 ± 2.21), (60.85 ± 1.91), (60.85 ± 1.91) and (2.91 ± 0.50), (2.17 ± 0.26) gL-1, ALB: (21.70 ± 2.18), (25.93 ± 2.74) and (25.00 ± 2.64) gL- (2.12 ± 0.31) mmol.L-1, triglyceride (1.05 ± 0.29), (0.49 ± 0.12) and (0.61 ± 0.15) mmol.L-1 respectively. The blood pressure, serum urea nitrogen (BUN) , Creatinine (SCr) (P <0.05 or P <0.01), and decreased the deposition of IgG in the mesangial area of rats. Conclusion: The establishment of nephrotic syndrome model by constant infusion of doxorubicin can improve the success rate of modeling and model stability. Zhenwu decoction can reduce urinary protein in NS rats, increase plasma protein level, reduce blood hypercoagulability and restore renal Function and glomerular structure, improve NS symptoms.