FTY720对大鼠肾小球硬化的作用及机制探讨

A study of FTY720 in prevention of glomerulosclerosis in rats and its mechanism

目的观察FTY720对5／6肾切除大鼠肾小球硬化的作用并探讨其作用机制。方法选择SD雄性大鼠24只，将其分为假手术组、模型组和FTY720治疗组，每组8只。后两组制作5／6肾切除肾小球硬化模型。末次手术后治疗组给予FTY720灌胃。术前、术后第8、12周取大鼠尾静脉血，采用计数板计算外周血淋巴细胞总数；第12周末处死大鼠后做常规病理检查和免疫组化检测，观察FTY720对肾小球中增殖细胞核抗原（PNCA）、p27、CD3表达的影响。结果治疗组外周血淋巴细胞计数较肾硬化组明显减少。治疗组大鼠肾小球病理损害明显减轻。免疫组化显示，与肾硬化组相比，治疗组PCNA表达明显减弱，p27蛋白表达升高。结论FTY720能减少肾小球内淋巴细胞浸润、上调p27蛋白、下调PCNA的表达，减轻肾小球细胞增殖，延缓肾小球硬化的进展。

Objective To study the effect of FTY720 on glomerulosclerosis in subtotal nephrectomized rats, and the underlying mechanism of FTY7720 in retarding the progression of glomerulosclerosis. Method 24 SD male rats were divided into sham-operation group, glomerulosclerosis model group and glomerulosclerosis treated with FTY720 group, 8 rats in each group. The rats in later two groups were subjected to 5/6 nephrectomy. After operation, the rats in treatment group were fed with FTY720 at dosage of 0. 5 mg·d^-1 for 12 weeks. Blood lymphocytes were counted before and 8, 12 w after operation. Then, the rats were sacrificed and the left kidney was subjected to pathological evaluation. The expression of PCNA, p27 and CD3 were determined by immunohistochemistry methods. Results Treatment with FTY720 significantly lowered the severity of glomerulosclerosis, blood lymphocyte count and renal lymphocyte infiltration. Compared with model group, a significant lower expression of glomerular PCNA and higher p27 protein expression were found in the FTY720 treated group （P〈0. 05）. Conclusions FTY720 can decrease lymphocyte infiltration in glomeruli, upregulate p27 expression and downregulate PCNA expression in glomeruli, thus alleviate the cell proliferation and prevent the progression of glomerulosclerosis in rats.