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

王丽敏; 李春玉; 张佳滨; 王禹; 迟瑛娇; 袁婧玮; 张颖杰

doi:10.7499/j.issn.1008-8830.2013.12.024

PDF(3995 KB)

中国当代儿科杂志 ›› 2013, Vol. 15 ›› Issue (12) : 1134-1138. DOI: 10.7499/j.issn.1008-8830.2013.12.024

论著·实验研究

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

王丽敏, 李春玉, 张佳滨, 王禹, 迟瑛娇, 袁婧玮, 张颖杰

作者信息 +

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

WANG Li-Min, LI Chun-Yu, ZHANG Jia-Bin, WANG Yu, CHI Ying-Jiao, YUAN Jing-Wei, ZHANG Ying-Jie

Author information +

文章历史 +

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.

导出引用

王丽敏, 李春玉, 张佳滨, 王禹, 迟瑛娇, 袁婧玮, 张颖杰. 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[J]. 中国当代儿科杂志. 2013, 15(12): 1134-1138 https://doi.org/10.7499/j.issn.1008-8830.2013.12.024

WANG Li-Min, LI Chun-Yu, ZHANG Jia-Bin, WANG Yu, CHI Ying-Jiao, YUAN Jing-Wei, ZHANG Ying-Jie. Effect of IL-18BP on Fractalkine chemokine expression in the kidney tissue of rats with renal fibrosis[J]. Chinese Journal of Contemporary Pediatrics. 2013, 15(12): 1134-1138 https://doi.org/10.7499/j.issn.1008-8830.2013.12.024

参考文献

[1] Koziolek MJ, Muller GA, Zapf A, Patschan D, Schmid H, Cohen CD, et al. Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure[J]. Nephrol Dial Transplant, 2010, 25(3): 684-698.
[2] Klahr S, Morrissey J. Obstructive nephropathy and renal fibrosis[J]. Am J Physiol Renal Physiol, 2002, 283(5): F861-F875.
[3] Yang XP, Mattagajasingh S, Su S, Chen G, Cai Z, Fox-Talbot K, et al. Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway[J]. Circ Res, 2007, 9(10): 1001-1008.
[4] Saederup N, Chan L, Lira SA, Charo IF. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2-/-mice: evidence for independent chemokine functions in atherogenesis[J]. Circulation, 2008, 117(13): 1642-1648.
[5] 常贺, 李刚, 张乐, 邹军, 朱铉, 金鑫. IL-18, IL-12 及相关因子在大鼠实验性自身免疫心肌炎心肌中的表达时程和特征[J]. 免疫学杂志, 2010, 26(6): 502-506.
[6] 姜红堃, 罗钢, 姜红. 白细胞介素18在激素耐药型肾病综合征外周血单个核细胞中的表达及意义[J]. 中国当代儿科杂志, 2009, 11(5): 337-340.
[7] 王丽敏, 亚瑟尔. IL-18BP联合泼尼松治疗阿霉素肾病大鼠的实验研究[J]. 黑龙江医药科学, 2012, 35(3): 1-3.
[8] Wang J, Long Q, Zhang W, Chen N. Protective effects of exogenous interleukin 18-binding protein in a rat model of acute renal ischemia-reperfusion injury[J]. Shock, 2012, 37(3): 333-340.
[9] Bani-Hani AH, Leslie JA, Asanuma H, Dinarello CA, Campbell MT, Meldrum DR, et al. IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis[J]. Kidney Int, 2009, 76(5): 500-511.
[10] 王丽敏, 邓李玲, 郑婵娟, 赵塔娜, 邹艳红, 李春玉. 白介素-18结合蛋白对阿霉素肾病大鼠Fractalkine表达的影响[J]. 临床儿科杂志, 2012, 30(7): 666-669.
[11] Wyburn KR, Chadban SJ, Kwan T. Interleukin-18 binding protein therapy is protective in adriamycin nephropathy[J]. Am J Physiol Renal Physiol, 2013, 304(1): F68-F76.