FTY720对单侧输尿管梗阻大鼠肾小管周围毛细血管的保护作用

目的 观察单侧输尿管梗阻大鼠模型中肾小管周围毛细血管(PTC)病变情况及FTY720对其干预作用.方法 采用单侧输尿管结扎术建立肾间质纤维化模型,将45只SD大鼠随机分为假手术组、模型组和FTY720治疗组.FTY720治疗组术前3d予0.2g·L-1FTY7200.5 mg·kg-1 ·d-1灌胃,假手术组和模型组予等量9 g·L-1盐水.每组分别于术后7、14、21 d各处死5只大鼠,处死前收集血清和24h尿液,观察肾功能和24h尿蛋白变化.取梗阻侧肾行组织学检查,观察肾间质纤维化程度和炎性细胞浸润情况.免疫组织化学方法检测其肾组织CD141、α-平滑肌肌动蛋白(α-SMA)、Ⅲ型胶原(COLⅢ)的表达水平.结果 与假手术组比较,模型组大鼠肾功能下降、肾间质纤维化明显,肾间质大量炎性细胞浸润,α-SMA、COLⅢ表达明显增加,肾间质微血管病变严重,术后7、14、21 d PTC密度分别为(116.80±8.92) mm-2、(98.80±3.96) mm-2、(62.20±7.01) mm-2(Pa＜0.05).与模型组比较,FTY720治疗组大鼠肾功能下降程度轻,肾间质浸润细胞数明显减少,肾间质纤维化程度、α-SMA、COLⅢ表达明显减少,且术后7、14、21 d PTC密度均高于模型组,分别为(132.50±8.32) mm-2、(119.40±12.21)mm-2、(85.00±2.59) mm-2 (Pa＜0.05).PTC密度与肾小管间质纤维化程度、肾间质炎性细胞浸润数、血清肌酐、BUN、24h尿蛋白量均呈负相关(r=-0.75、-0.72、-0.64、-0.65、-0.67,Pa＜0.01).结论 FTY720能明显减少单侧输尿管梗阻大鼠肾间质炎性细胞浸润及肾间质毛细血管丢失,保护肾功能,减轻肾间质纤维化程度.

Protection of FTY720 on Peritubular Capillary in Unilateral Ureteral Obstruction Rats

Objective To observe the protection of FTY720 on peritubular capillary(PTC)loss in unilateral ureteral obstruction(UUO)rats. Methods UUO was induced in SD rats by ligation of the left ureter.Forty-five male SD rats were randomly divided into sham-operated group,UUO group and FTY720 treatment group.The rats in FTY720 treatment group were gavaged with 0.5 mg·kg-1·d-1 of FTY720,which begun 3 days before operation.The rats in sham group and UUO group were gavaged with equal volume saline water of 9 g·L-1.Five rats in each group were sacrificed on the 7th,14th and 21st day after UUO or sham-operation.Before being sacrificed,24 h urine protein,blood urea nitrogen and serum creatinine were determined.Tubulointerstitial fibrosis and inflammatory cell infiltration were examined by morphological analysis,while the expressions of CD141,α-smooth muscle actin(α-SMA),and collagenⅢ were detected by immunohistochemical me-thod and scored semi-quantitatively. Results Significant interstitial fibrosis,renal function deterioration and higher expressions of α-SMA,collagenⅢ in the tubulointerstitial region were noted in UUO group with more markedly decreased PTC density,compared with sham-operated group.The PTC density were(116.80±8.92) mm-2,(98.80±3.96)mm-2,and(62.20±7.01) mm-2 on the 7th,14th,and 21st day(Pa<0.05).Compared with UUO group,interstitial fibrosis and impaired renal function were ameliorated by the administration of FTY720 with less PTC loss.The PTC density were(132.50±8.32) mm-2,(119.40±12.21) mm-2,and(85.00±2.59) mm-2 on the 7th,14th,and 21st day(Pa<0.05).It showed that PTC density was negatively correlated with the degree of renal fibrosis,the number of inflammatory cells,the level of serum creatinine and urea nitrogen,and 24 h urine protein(r=-0.75,-0.72,-0.64,-0.65,-0.67,Pa<0.01). Conclusions FTY720 can reduce infiltration of inflammatory cell,prevent the loss of PTC,and protect renal function and thus ameliorate renal interstitial fibrosis.