尿毒清对阿霉素肾病大鼠致纤维化因子表达的影响

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24?h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OPN mRNA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。

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

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( TOF-β_1 ) , tissue inhibition of metalloproteinase-1 ( T1MP-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-β_1 , TTMP-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-β_1 , 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.