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慢性肾功能衰竭(CRF)是一种进行性慢性肾脏疾病,并伴随着物质排泄的改变.然而,在CRF后肾脏排泄通道的变化尚不明确.本研究的目的是评价CRF后大鼠体内内源性和外源性物质肾脏排泄的变化.结果显示,在腺嘌呤(50和100 mg/kg)诱导的CRF大鼠中血清胱抑素C、肌酐和尿素氮水平显著增加,肾脏转运体rOCT2表达剂量依赖性增加,rMRP2和rMATE1水平剂量依赖性降低,rMPR4水平在腺嘌呤(50 mg/kg)诱导的CRF大鼠中显著增加.与正常大鼠相比,在腺嘌呤(100mg/kg)诱导的CRF大鼠中血浆二甲双胍、对氨基马尿酸和呋塞米的浓度显著增加.然而,在腺嘌呤(50mg/kg)诱导的CRF大鼠血中二甲双胍和对氨基马尿酸浓度没有明显的改变.与此一致,在腺嘌呤(50 mg/kg)诱导的CRF大鼠中二甲双胍和对氨基马尿酸的尿排泄也未发生明显的改变.此外,腺嘌呤(50和100 mg/kg)诱导的CRF大鼠肾脏N1-甲基烟酰胺摄取增加,腺嘌呤(50 mg/kg)诱导CRF大鼠肾脏苯基-β-D-葡萄糖醛酸和马尿酸摄取增加.这些结果表明腺嘌呤(100 mg/kg)诱导的CRF大鼠中肾脏GFR-rOCTs-RMAT1和GFR-rOAT1/rOAT3-rMRP通路功能降低,而腺嘌呤(50 mg/kg)诱导的CRF大鼠中肾小管rOCTs-RMAT1和rOAT1-MRPs通路转运功能增加.“,”Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats.Results showed that the levels of cystatin C,creatinine,and urea nitrogen were dramatically increased in the adenine(50 or 100 mg/kg)-induced CRF rats.The levels of rOCT2 were dose-dependently up-regulated by adenine,and rMRP2 and rMATE1 levels were dose-dependently down-regulated,while rMRP4 was induced by adenine(50).Plasma concentrations of metformin,p-aminohippurate,and furosemide in the adenine(100)group were significantly increased compared with the control group.However,plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine(50)group.Consistently,urinary excretions of metformin and p-aminohippurate were unaffected.In addition,renal N1-methylnicotinamide uptakes were increased in rats treated with adenine,and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine(50).These results showed that adenine(100)-induced CRF caused the reduced function of GFR-rOCTs-rMATE1 and GFR-rOAT1/rOAT3-rMRP pathway,and oppositely the renal tubular transport pathways of rOCTs-rMATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine(50).