尿毒清对阿霉素肾病大鼠致纤维化因子表达的影响

Effects of Niaoduqing on expressions of the fibrogenetic factors in rats with Adriamycin nephropathy

目的观察尿毒清对阿霉素(ADR)肾病大鼠肾脏转化生长因子-β1(TGF-β1)、金属蛋白酶1组织抑制剂(TIMP-1)、纤溶酶原激活物抑制物1(PAI-1)和骨调素(OPN)mRNA表达的影响,探讨尿毒清治疗慢性肾脏疾病的机制。方法成年雄性SD大鼠24只,采用单侧肾切除加重复尾静脉注射ADR的方法制作ADR肾病模型,随机分为正常组(N组)、模型组(M组)、尿毒清组(Ni组)、贝那普利组(B组)4组,每组6只。用药第4、8周后观察各组大鼠24h尿蛋白定量、血脂、血浆总蛋白(TP)、血浆白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)的水平,实时荧光定量PCR测定第8周肾组织中TGF-β1、TIMP-1、PAI-1及OPN mRNA的表达。结果尿毒清和贝那普利均能减少ADR肾病大鼠尿蛋白,降低BUN、Scr,升高血浆蛋白,纠正脂代谢紊乱,减少TGF-β1、TIMP-1、PAI-1及OPNmRNA的表达,与M组相比有显著差异(P<0.01);而Ni组PAI-1 mRNA水平较B组显著降低(P<0.01)。结论尿毒清可下调ADR肾病大鼠肾脏组织TGF-β1、TIMP-1、PAI-1及OPN mRNA的合成,可能是其治疗慢性肾脏疾病的重要机制之一。

Objective To explore the mechanisms of the beneficial effects of Niaoduqing,and to investigate the effects of Niaoduqing on expressions of renal transforming growth factor-betal,and tissue inhibition of metalloproteinase-1,plasminogen activator inhibitor-1 and osteopontin mRNAs in rats with Adriamycin-induced nephropathy.Methods The male rats were randomly divided into four groups：the normal group（N group）,the model group（M group）,the Niaoduqing group（Ni group）and the Benazepril group（B group）.24-hour urinary protein excretion and renal function were determined at 4 and 8 weeks.Expressions of transforming growth factor-betal（TGF-β1）,tissue inhibition of metalloproteinase-1（TIMP-1）,plasminogen activetor inhibitor-1（PAI-1）and osteopontin（OPN）mRNA were determined by real-time quantitative RT-PCR.Results Niaoduqing and Benazepril effectively reduced the levels of 24-hour urinary protein excretion,Bun,and Scr,elevated protein levels,corrected fat metabolic disorder,and down-regulated expressions of TGF-β1,TIMP-1,PAI-1 and OPN mRNAs（P〈0.01）compared with the M group.Niaoduqing could significantly inhibit expression of PAI-1 mRNA compared with that of Benazepril（P〈0.01）.Conclusion Niaoduqing can down-regulate expressions of TGF-β1,TIMP-1,PAI-1 and OPN mRNAs in renal tissues of rats with Adriamycin-induced nephropathy,which may be its active mechanism in treating chronic renal diseases.