中文摘要：

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（cyclinE，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（28．64±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）μmol／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24h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C01-IV、FN聚积有关。

英文摘要：

Objective To study the effect of FTY720 on glomerulosclerosis and expression of cell cycle regulatory proteins in subtotal nephrectomized rats. Methods Twenty-four rats were divided into sham-operation group, glomerulosclerosis model group and FTY720 treated glomerulosclerosis group with 8 rats in each group. The rats in the latter two groups were subjected to subtotal nephreetomy. After operation, the FTY720 treated group was fed with FTY720 at a dose of 0. 5 mg/（kg · d） for 12 weeks. Urine protein excretion was measured before operation and 2 w, 4 w, 8 w and 12 w after operation. Then the rats were sacrificed and the left kidney was subjected to pathological evaluation. The expression of collagen IV, fibroneetin, and eyelin E, p21, p27 were determined by immunohistochemieal methods. Results Compared with the control group, the model group showed higher daily urine protein （Up） excretion from 2 w, （8. 07±1. 61 ） mg/d and thereafter. At 12 w, Up increased to （28.60±12. 21 ） mg/d in model group, significantly higher than that in control group （ P 〈 0. 05 ）. After treatment with FTY720, Up began to decrease from 4 w after operation, （9.90 ± 1.49 ） mg/d at that time and （ 11.35 ± 2.09 ） mg/d at 12 w, beth were significantly lower than those in model group （P 〈 0. 01 ）. The model group showed higher level of serum ereatinine from 8 w, （61.08±4.28） p, mol/L at that time, （ 130. 20±23.90） p, mol/L at 12 w, beth were much higher than those in control group （ P 〈 0. 05 ）. In FTY720 treated group, serum ereatinine level was （80. 19 ±7. 11） μmol/L at 12 w, much lower than that in model group. The changes of BUN weresimilar to those of creatinine in each group. Renal pathology and immunohistological evaluation showed that FTY720 could significantly inhibit the expression of collagen-IVand fibronectin in glomeruli and attenuate the extent of glomerulosclerosis. Moreover, FTY720 could upregulate glomerular expression of p21 and downregulate glomerular expression o