摘要
目的:观察阿霉素肾病大鼠肾皮质nephrinmRNA的表达及来氟米特对其表达的影响,探讨nephrin在蛋白尿发生发展中的作用以及来氟米特治疗肾脏病的可能机制。方法:建立阿霉素肾病模型,第4周进一步将模型组分为治疗组和非治疗组,治疗组给予来氟米特管饲。应用光镜、电镜观察不同时期(第2、4、6、8周)各组大鼠肾组织的病理改变;BCA法检测尿蛋白排泄量;半定量RT-PCR的方法检测肾皮质中nephrinmRNA的表达。结果:(1)模型组尿蛋白量逐渐增加,而治疗组第6周和第8周的尿蛋白量均低于同时期的非治疗组水平(P=0.02和P<0.01);(2)模型组nephrinmRNA表达量在2、4、6、8周分别为对照组的0.5、1.0、2.0、1.6倍,并与尿蛋白量呈正相关(r=0.699,P<0.001);(3)模型治疗组nephrinmRNA的表达第8周达非治疗组的1.3倍。结论:(1)随着阿霉素肾病大鼠尿蛋白排泄量的增加,肾皮质nephrinmRNA的表达发生了显著变化,并与蛋白尿的发生发展之间具有一定的相关性;(2)来氟米特可减少肾病大鼠尿蛋白量,同时增加肾皮质nephrinmRNA的表达。
Objective:To investigate the expression of nephrin mRNA in rats with adriamycin nephropathy, and to explore the effects of leflunomide on proteinuria in rats with adriamycin nephropathy and on the expression of nephrin mRNA. Methods: Thirty-five SD rats, weighted from 140 to 160 g, were randomly divided into the nephropathy model group and normal control group. The nephropathy model was established by a single intravenous injection of adriamycin (6 mg/kg body weight). While the normal control group received only 0.9% sodium chloride solution with the same volume. From the beginning of the 5th week after injection, ten nephropathy rats were given leflunornide (10 mg·kg^-1·d^-1)) by gavages. At the end of the 2nd, 4th, 6th and 8th week after injection, the rats were sacrificed and the renal cortex was acquired. Urine was collected overnight in metabolic cages and the amount of proteinuria was measured with BCA protein assay kit. The semiquantitative RT- PCR was used for detecting the levels of nephrin mRNA. Results: (1)In the nephropathy groups, nephrin mRNA level decreased by 50% at the 2nd week,and the control level was reached at the 4th week, and it showed 2 - and 6 - fold up - regulation at the 6th and 8th week, respectively. The expression of nephrin mRNA was Fositively correlated with the amount of proteinuria ( r = 0. 699, P 〈 0.001 ). (2) The amount of proteinuria in leflunomide-treated nephropathy rats was significantly lower than that in non-treated nephropathy rats. In leflunornide-treated nephropathy rats, nephrin mRNA level in the 8th week group was 1.3 times of that in non-treated nephropathy rats. Conclusion:The change in the expression of nephrin mRNA is to some extent related to the development of proteinuria in adriamycin nephropathy rats. Leflunomide reduces proteinuria in adriamycin nephropathy rats, and its effects may be by regulating the expression of nephrin mRNA.
出处
《中国中西医结合肾病杂志》
2007年第1期10-13,F0002,共5页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
江苏省医学重点人才工程(135)基金资助项目(No.RC2002045)