来氟米特对局灶节段性肾小球硬化大鼠转化生长因子-β1表达水平的影响

Effects of leflunomide on expression of transforming growth factor-β1 in focal segmental glomerulosclerosis rats

目的通过观察来氟米特对局灶节段性肾小球硬化（FSGS）大鼠肾组织转化生长因子（TGF）-β1表达水平变化的影响，探讨来氟米特对肾脏保护作用的可能机制。方法将24只sD大鼠按体质量简单随机分3组：正常对照组、FSGS模型组、来氟米特治疗组，每组各8只大鼠。采用单侧肾切除l周后重复注射多柔比星法建立FSGS模型。术后2周起，来氟米特治疗组给予来氟米特混悬液5mg／（kg·d）灌胃，正常对照组、FSGS模型组给予等量溶媒灌胃。于实验第8周末将各组大鼠处死并收集标本，记录血肌酐、尿素氮、总胆固醇、清蛋白及24h尿蛋白排泄量；取。肾组织行病理检查并计算肾小球硬化指数（GSI）；免疫组织化学法检测TGF—β1在肾脏的表达；Westernblot检测TGF-β1在肾组织的蛋白表达。结果与正常对照组比较，FSGS模型组及来氟米特治疗组大鼠24h尿蛋白排泄量、血肌酐、尿素氮、胆固醇均显著升高，而血清清蛋白则明显降低，肾组织病理改变较重且TGF—β1蛋白表达明显升高，差异均有统计学意义（P均〈0．05）；与FSGS模型组比较，于实验第8周末，来氟米特治疗组大鼠24h尿蛋白排泄量、相关血清生化指标及肾组织病理改变均有不同程度改善，且肾组织TGF—β1蛋白表达下降，差异均有统计学意义（P均〈0．05）。结论来氟米特可通过抑制TGF—β1的表达，减轻FSGS肾组织纤维化程度，从而保护。肾脏。

Objective To explore the possible mechanisms of the protective effect of leflunomide on kidneys by observing the effects of leflunomide on rat kidney tissue of focal segmental glomerulosclerosis （ FSGS ） expression level of transforming growth factor （ TGF ） β1. Methods Twenty-four SD rats were randomly divided into 3 groups ： normal control group （ n = 8 ） , FSGS model group （ n = 8 ） and leflunomide treatment group （ n = 8 ）. Unilateral nephrec- tomy 1 week after repeated injection of doxorubicin established FSGS model. Since 2 weeks after surgery,the treatment group had been given the leflunomide suspension 5 mg/（ kg ~ d ） orally, while normal control group and model group had been given the same amount of solvent orally. In the 8th week of the experiment,the rats were sacrificed and the specimens were collected,so serum creatinine, blood urea nitrogen, total cholesterol, albumin and 24 hours urinary pro- tein were recorded ; renal tissue was taken for pathological examination and calculation of glomerular sclerosis index （GSI） was made;immunohistochemical detection of TGF-β1 expression in the kidney was performed;The expression of TGF-β1 was examined by Western blot. Results Compared with normal control group, FSGS model group and lefluno- mide treatment group rats＇ 24 hours urinary protein excretion, serum creatinine, blood urea nitrogen, and cholesterol sig- nificantly increased while serum albumin significantly reduced severe renal pathological changes and TGF-β1 protein expression was significantly increased, and the differences were statistically significant （ all P 〈 0.05 ） ; Compared with the FSGS model group,in the 8th weekend of the experiments,the treated rats＇ 24 hours urinary protein excretion,rele- vant serum biochemical indicators of renal pathological changes had different degrees of improvement in renal tissue and TGF-β1 protein expression was decreased, so the differences above were statistically significant （all P 〈 0.05 ）. Conclu- sions Leflunomide may reduce the FSGS kidney tissue fibrosis by inhibiting the expression of TGF-β1 ,and thus pro- tect the kidneys.