白细胞介素-17A在大鼠肾缺血再灌注损伤中的作用

Effect of interleuldn- 17A on renal ischemiareperfusion injury in rats

目的探讨白细胞介素（IL）-17A在大鼠肾缺血再灌注（I／R）损伤中的作用及其机制。方法将60只雄性SD大鼠随机分为3组：假手术组（S组）、缺血再灌注组（I／R组）和IL-17A抗体预处理组（抗IL-17A＋I／R组），每组20只。采用夹闭双侧肾蒂（30min）的方法制备肾I／R损伤大鼠模型，再灌注6h后处死大鼠，分别收集血清和肾组织样本，检测血肌酐（SCr）、血尿素氮（BUN）水平，检测血清IL-17A、肿瘤坏死因子（TNF）-α、细胞间黏附分子（ICAM）-1的表达，检测肾组织髓过氧化物酶（MPO）的活性，肾组织苏木素-伊红（HE）染色后观察组织形态变化并行肾小管损伤评分。结果与S组比较，I／R组的SCr、BUN水平均升高，差异有统计学意义（P〈0．05），抗IL-17A＋I／R组BUN水平升高（P〈0．05）、SCr水平无统计学意义（P〉0．05）；S、I／R及抗IL-17A＋I／R组血清IL-17A水平分别为（4．20±2．24）、（239．50±18．72）和（17．95±13．61）ng／L，L／R、抗IL-17A＋I／R组水平较S组均显著升高（P〈0．05），抗IL-17A＋I／R组水平较I／R组显著下降（P〈0．05），TNF-α、ICAM-1水平及肾组织MPO活性显示了与IL-17A水平相同的变化趋势；S、I／R及抗IL-17A＋I／R组肾小管损伤评分分别为（2．14±1．02）、（16．41±3．71）和（5．83±2．15）分，I／R、抗IL-17A＋I／R组评分较S组升高（P〈0．05），抗IL-17A＋I／R组评分较I／R组降低（P〈0．05）。结论IL-17A在大鼠肾脏I／R损伤中发挥关键作用，阻断IL-17A能减少炎性因子释放和中性粒细胞在肾组织的聚集，减轻肾损伤。

Objective To investigate the effects of interleukin （IL） - 17A expression on renal is- chemia - reperfusion injury in rats and the mechanism. Methods Sixty male SD rats were randomly divided into 3 groups ： sham - operated group （ S group, n = 20）, ischemia - reperfusion group （ I/R group, n = ：20） and anti - IL - 17 A antibody - treated group （ anti - IL - 17A ＋ I/R group, n = 20 ）. Both renal pedi- cales of rats were clamped for 30 rain to make the animal models of renal ischemia - repeffusion injury. The plasma and kidneys were collected for detecting the serum creatinine （SCr） and blood urea nitrogen （BUN）. The expression of IL- 17 A, tumour necrosis factor （TNF） -α and intercellular adhesion molecule （ ICAM ） - 1 in serum was detected by enzyme - linked immunosorbent assay. Myeloperoxidase （MPO） of kidney tissues was determined. Histopathological changes of kidney tissues were observed by hematoxylin eosin （HE） staining, and the damage degree was evaluated by Paller scoring method. Results The levels of SCr and BUN in I/R group were significantly higher （P 〈 0. 05 ）, and the levels of BUN in anti - IL - 17A ＋ I/R group was significantly higher than in S group. There was no significant difference in SCr level between anti -IL- 17A ＋ I/R group and S group （P 〉0. 05）. The levels of IL- 17A in S, I/R and anti - IL - 17A ＋ I/R groups were （4. 20 ±2. 24）, （239. 50 ± 18. 72） and （ 17. 95 ± 13.61 ） ng/L respectively. The level of IL - 17A in I/R and anti - IL - 17A ＋ I/R groups was significantly higher than in S group （P 〈0. 05）. The level of IL- 17A in anti -IL- 17A ＋ I/R group was significantly decreased as compared with I/R group （ P 〈 0.05 ）. The levels of TNF - α and ICAM - 1 in serum, and activity of MPO in kidney tissues showed the same tendency of changes as IL - 17A. The score of kidney injury in S, I/R and anti - IL - 17A ＋ I/R groups was 2. 14 ± 1.02, 16.41±3.71 and 5.83±2. 15 respectively. The score in anti - IL - 17A ＋ I/R group was significantly decreased as compared with I/R group （ P 〈 0.05 ）. Conelusiou IL - 17A plays critical role in rat renal ischemia - reperfusion injury. IL - 17A antibody blockade could decrease the level of inflammatory factors, inhibit the movement of nentrophils, and reduce the renal damage.