白细胞介素1受体拮抗剂对大鼠肾间质纤维化干预作用的研究

目的:动态观察白细胞介素1受体拮抗剂(IL-1ra)对单侧输尿管梗阻模型大鼠肾间质纤维化及肾功能的影响。方法:将72只大鼠随机等分为3组:假手术(SOR)组、单侧输尿管结扎(UUO)组和IL-1ra处理(Tre)组,UUO组和Tre组制备UUO模型,SOR组术式同UUO组但不结扎输尿管。Tre组每天给予的10%IL-1ra溶液腹腔注射,而另两组则腹腔注射等体积无菌注射用水。各组分别在术后第1、3、7和14天随机处死6只大鼠,采血并取梗阻侧肾脏,行HE和Masson染色观察肾组织病理变化,免疫组化检测肾组织a-SMA的表达,同时检测血液中肌酐、尿素氮的含量。结果:随着梗阻时间的延长,UUO组与Tre组肾间质纤维化的程度均高于SOR组,肾功能具有先恶化后好转的趋势(P<0.05);与UUO组相比,Tre组肾间质纤维化程度有所减轻,肾功能好转趋势也较UUO组明显,其差异从第7天起具有统计学意义(P<0.05)。结论:IL-1ra可延缓梗阻性肾间质纤维化进程,这一作用可能与其抑制白细胞介素1的促纤维化作用有关。

The Effect of Interleukin-1 Receptor Antagonist on Renal Interstitial Fibrosis in Rats

Objective: To observe the influence of interleukin-1 receptor antagonist(IL-1ra) on renal interstitial fibrosis and renal function induced by unilateral ureteral obstruction.Method: 72 rats were randomly divided into 3 groups: sham operation(SOR) group,unilateral ureteral ligation(UUO) group and IL-1ra treatment(Tre) group.The unilateral ureteral obstruction operation was performed with the UUO group and the Tre group,the same operation was performed with SOR group,but ureter wasn’t tied up.The rats in Tre group were injected 10% IL-1ra solution per day,while rats in the other two groups were injected equal volume of sterile water.At the 1th,3th,7th and 14th days after operation there were 6 rats of each group were killed,their blood and obstructed kidneys were collected for creatinine and urea nitrogen detection,HE and Masson staining and immunohistochemistry,which would reveal the level of renal interstitial fibrosis and renal function.Result: Along with obstruction time extension,The UUO group and the Tre group kidney mesenchymal fibrosis’s degree were higher than the SOR group,and the tendency which after the kidney function has worsen first,changed for the better(P<0.05);The Tre group kidney mesenchymal fibrosis degree has reduced,the kidney function change for the better tendency also compares the UUO group to be obvious,The difference has statistics significance from the 7th day(P<0.05).Conclusion: IL-1ra has therapeutic effect on renal interstitial fibrosis,which may be associated with inhibition of interleukin-1.