论文部分内容阅读
目的观察 FTY720对肾大部切除大鼠肾小球硬化的作用,探讨其作用机制。方法采用。肾大部切除制作肾小球硬化模型,分模型组和 FTY720治疗组,设假手术组为正常对照组,每组8只。检测各组术前及术后第2、4、8、12周大鼠24h 尿蛋白,术前及术后8周、12周检测血尿素氮和肌酐以及残肾组织病理改变,并应用免疫组化方法检测Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)的表达水平及细胞周期调控蛋白 p21、p27、细胞周期素 E(cyelinE,CE)的表达。结果模型组术后2周24h尿蛋白升高至(8.07±1.61)mg/d,以后逐渐增高,12周达(28.6±12.21)mg/d,治疗组24h 尿蛋白量在术后4周为(9.90±1.49)mg/d,12周时为(11.35±2.09)mg/d,较模型组减低(P<0.01)。与假手术组相比,模型组8周血肌酐升高达(61.08±4.28)μmol/L,12周时为(130.20±23.90)μ5mol/L,升高更明显(P<0.05);治疗组血肌酐则未见明显升高,12周时为(80.19±7.11)μmol/L,较模型组显著减低(P<0.05);各组血尿素氮与肌酐变化相似。肾脏病理和免疫组化染色显示,FTY720能明显减轻大鼠硬化程度,抑制肾小球内细胞外基质 Col-Ⅳ、FN 的表达。细胞周期调控蛋白研究结果表明 FTY720能升高肾小球 p27表达,降低 p21及 CE 表达。治疗组 p21和 CE 表达明显低于模型组,但仍稍高于假手术组,p27明显高于模型组,与正常组无明显区别。结论 FTY720能显著降低肾大部切除大鼠的24 h 尿蛋白量,防止。肾小球硬化,其作用与调控细胞周期调节蛋白的表达,减少Col-Ⅳ、FN 聚积有关。
Objective To observe the effect of FTY720 on glomerulosclerosis in rats with subtotal nephrectomy and to explore its mechanism. Method used. Renal resection of glomerulosclerosis model, sub-model group and FTY720 treatment group, the sham-operated group as the normal control group, 8 in each group. The 24h urinary protein in preoperative, postoperative, 2nd, 4th, 8th and 12th week of each group were measured, blood urea nitrogen, creatinine and residual kidney pathological changes were detected before operation, 8 weeks and 12 weeks after operation, Methods The expressions of type Ⅳ collagen and fibronectin (FN) and the expression of cell cycle regulatory proteins (p21, p27, cyelinE, CE) were detected. Results Urinary protein increased to (8.07 ± 1.61) mg / d at 2 weeks after operation in the model group, then gradually increased at 12 weeks (28.6 ± 12.21) mg / d. The proteinuria of 24 hours in the treatment group was (9.90 ± 1.49) mg / d and (11.35 ± 2.09) mg / d at 12 weeks respectively, which was lower than that of model group (P <0.01). Compared with the sham-operation group, the serum creatinine in model group increased by (61.08 ± 4.28) μmol / L at 8 weeks and (130.20 ± 23.90) μ5mol / L at 12 weeks, Creatinine was not significantly increased at 12 weeks (80.19 ± 7.11) μmol / L, compared with the model group was significantly lower (P <0.05); blood urea nitrogen and creatinine changes were similar in all groups. Kidney pathology and immunohistochemical staining showed that FTY720 can significantly reduce the degree of sclerosis in rats and inhibit the expression of extracellular matrix Col-Ⅳ, FN in glomeruli. The results of cell cycle regulatory proteins showed that FTY720 increased the expression of p27 in glomeruli and decreased the expression of p21 and CE. The expression of p21 and CE in the treatment group was significantly lower than that in the model group, but still slightly higher than that in the sham operation group. The level of p27 in the treatment group was significantly higher than that in the model group. There was no significant difference between the two groups. Conclusion FTY720 can significantly reduce the amount of 24 h urine protein in rats with subtotal nephrectomy and prevent it. Glomerulosclerosis, its role and regulation of cell cycle regulatory protein expression, reduce Col-Ⅳ, FN accumulation related.