分形素趋化因子在肾脏纤维化大鼠肾组织中的表达及IL-18结合蛋白对其表达的影响

Effect of IL-18BP on Fractalkine chemokine expression in the kidney tissue of rats with renal fibrosis

摘要:

目的 探讨分形素趋化因子（FKN）在肾脏纤维化大鼠肾组织中的表达情况及IL-18结合蛋白（IL-18BP）对其在肾组织内表达的影响。方法 将雄性Wistar大鼠随机分为假手术组（n=24）、单侧输尿管梗阻模型组（模型组，n=22）和IL-18BP治疗组（治疗组，n=23）。采用单侧输尿管结扎方法造模，假手术组分离输尿管但不结扎，治疗组于造模成功后每隔1日腹腔注射1次IL-18BP（0.1 mg/kg），共7次，模型组和假手术组腹腔注射等量生理盐水。每组分别在腹腔注射完成后3 d、7 d和14 d各处死7~8只大鼠，采用免疫组织化学法和Western blot印迹法检测各组大鼠不同时间点肾组织FKN的表达水平。结果 同假手术组比较，不同时间点模型组肾组织FKN的表达量均明显升高（均P<0.01）；同模型组比较，不同时间点治疗组肾组织FKN表达水平均明显降低（均P<0.01）。结论 肾脏纤维化大鼠肾组织FKN表达水平明显增高；IL-18BP特异性拮抗IL-18后，可能通过FKN途径延缓肾脏纤维化的发生发展。

Abstract:

Objective To study the expression of Fractalkine (FKN) in the kidney tissue of rats with renal fibrosis and the effect of IL-18BP on FKN. Methods Male Wister rats were randomly assigned to sham-operation (n=24), unilatral ureteral obstruction (UUO, n=22), and IL-18 binding protein (IL-18BP) treatment groups (n=23). The UUO model was prepared by unilateral ureteral ligation in the later two groups. The IL-18BP treatment group received an intraperitoneal injection of IL-18BP (0.1 mg/kg) every other day after UUO inducement, for 7 times, while normal saline was administered in the other two groups. Seven or eight rats of every group were sacrificed at 3, 7 or 14 days after IL-18BP or normal saline injections. FKN levels at various times were detected by immunohistochemistry and Western blot. Results Compared with the sham-operation group, FKN levels in the kidney tissue of the untreated UUO group increased significantly at all time points (P<0.01). IL-18BP treatment decreased significantly FKN levels in the kidney tissue at all time points compared with the untreated UUO group (P<0.01). Conclusions IL-18BP treatment may down-regulate the increased FKN levels of the rat kidney tissue caused by UUO, possibly thus delays the occurrence and development of renal fibrosis.