白细胞介素17A在急性百草枯中毒小鼠肾损伤中的作用  

Effects of Interleukin-17A on Acute Paraquat-intoxication-induced Kidney Injury in Mice

作　　者：宋宏伟[1] 杨琛[1] 刘伟[1] 刘志[1] 

机构地区：[1]中国医科大学附属第一医院急诊科,沈阳110001

出　　处：《中国医科大学学报》2017年第5期392-396,400,共6页Journal of China Medical University

基　　金：国家自然科学基金(81571882);辽宁省科学技术计划(2013225303)

摘　　要：目的探讨白细胞介素17A(IL-17A)在急性百草枯中毒小鼠肾损伤中的作用及其机制。方法 72只ICR小鼠随机分为3组:生理盐水组(NS组)、百草枯中毒(PQ)组和抗体组(PQ+Ab组),每组24只。PQ与PQ+Ab组均采用一次性灌胃PQ溶液建立PQ中毒模型,PQ+Ab组于染毒2 h后一次性腹腔注射IL-17A抗体,NS组分别给予等量生理盐水。各组于染毒后8、24、48、72 h取6只小鼠处死,分别收集血清和肾组织样本,ELISA法检测血清IL-17A、血肌酐(SCr)、血尿素氮(BUN)水平,化学比色法检测肾组织髓过氧化物酶(MPO)活性,肾组织经苏木素-伊红(HE)染色后观察组织形态变化并评分,免疫组化法和实时定量PCR法分别检测IL-17A蛋白及m RNA的表达。结果与NS组比较,PQ与PQ+Ab组小鼠血清中IL-17A水平升高,肾组织中MPO活性增加,血SCr、BUN升高(均P<0.01);与PQ组比较,PQ+Ab组小鼠血清中IL-17A显著降低、肾组织中MPO活性降低、血SCr、BUN水平下降(均P<0.01),肾病理损伤减轻。结论 IL-17A可能通过活化、募集中性粒细胞促进急性PQ中毒小鼠肾损伤,抗体阻断IL-17A能减轻该损伤。Objective To investigate the effects of interleukin-17A on kidney injury induced by paraquat （PQ）. Methods Seventy-two ICR mice were randomly divided into 3 groups ： NS, PQ, and PQ＋Ab （n = 24 for each）. The PQ-poisoning model was established by administering a gavage of PQ solution;mice in the PQ＋Ab group were then administereda dose of anti-IL-17A antibody 2 hours later by i.p. injection, whereas the NS group were administered a corresponding volume of normal sahne instead.The mice were killed at 8,24,48, or 72 h to obtain renal tissues and serum. An enzyme-linked immunosorbent assay （ELISA） was used to determine serum IL- 17A, serum creatinine （SCr）, and blood urea nitrogen （BUN） levels.Chemical colorimetry was used to detect the viability of myelopemxidase （MPO） in renal tissue, and hematoxylin-eosin （HE） stain- ing was used to observe the renal pathologic changes. Immunohistochemistry （IHC） and PCR were used to examine IL-17A expression in renal tis- sues. Results Serum IL-17A, renal tissue MPO viabilities, BUN, and SCr were increased in the PQ and PQ＋Ab groups, compared to those in the NS group （P 〈 0.01 ）. However, the above-mentioned parameters were lower in the PQ＋Ab group than in the PQ group （P 〈 0.01 ）. Conclusion IL-17A promotes mouse kidney injury induced by acute PQ-intoxication through activating and/or recruiting neutrophils ; therefore, blockade IL- 17A with antibody can attenuate the injury.

关 键 词：白细胞介素17A 百草枯 中毒 肾损伤 小鼠 

分 类 号：R594.4[医药卫生—内科学]