IL-6、TNF-α及MKK3在小鼠急性肾损伤诱导的肺损伤中的表达及意义

Roles of IL-6,TNF-α and P38 Mapk Pathway in Acute Lung Injury Induced By Kidney Injury in Mice

【目的】探讨白细胞介素6（IL‐6）、肿瘤坏死因子‐α（TNF‐α）及丝裂原活化蛋白激酶（MKK3）在急性肾损伤诱导的肺损伤中的表达及意义。【方法】以36只 C57BL／6J 雄性6-8周龄小鼠为研究对象，随机分为三组：假手术模型16只（S 组）、缺血再灌注16只（IR 组）、对照组4只（C 组）。 C 组、S 组和 IR 组分别于6 h 、24 h 、48 h 、5 d 采用免疫组织化学染色方法检测肺 IL‐6、TNF‐α的表达；RT‐PCR 方法检测肺组织 IL‐6、TNF‐α及 MKK3 mRNA 水平的表达。【结果】C 组和 S 组肺组织各时间点的 IL‐6、TNF‐α蛋白、mRNA 水平的表达比较均无显著性差异（ P ＞0．05）；IR 组肺组织 IL‐6表达于再灌注后6 h 显著增高，并随着再灌注时间延长逐渐增强，48 h 达到峰值，5 d 回复基线水平。 MKK3的表达在对照组、假手术组各亚组小鼠肺组织间无显著性差异（ P ＞0．05），IR组再灌注后48 h 表达达峰值（与24 h 和6 h 相比，P ＜0．05），再灌注后5 d 表达明显降低（与6 h 、24 h 和48 h 相比，P ＜0．05）。 【结论】缺血再灌注肾损伤模型小鼠肺组织 IL‐6及 TNF‐α的表达与肺损伤时空密切相关，提示IL‐6及 TNF‐α是缺血再灌注肾损伤模型小鼠急性肺损伤的增恶因子；急性肾损伤诱导急性肺损伤可通过 p38 MAPK 途径介导的炎症反应而产生。

[Objective] To explore the roles of interleukin‐6 （IL‐6） ,tumor necrosis factor‐α （TNF‐α） and P38 MAPK pathway on acute lung injury after kidney ischemia‐reperfusion in mice and elucidate the mechanism of acute lung injury induced by acute kidney injury （AKI） .[Methods] A total of 36 male mice （C57BL/6J） were randomly divided into control ？ ,sham （S） and ischemia‐reperfusion （IR） groups .Both S and IR groups were sampled at 6h ,24h ,48h and 5d separately .Then immunohistochemistry was employed for detecting the protein expression levels of IL ‐6 and TNF‐α in lung tissue .And reverse transcription‐polymerase chain reaction （RT‐PCR） was used for measuring the mRNA expres‐sion levels of IL‐6 ,TNF‐α and MKK3 in lung tissue .[Results] The mRNA expression levels of IL‐6 ,TNF‐α and MKK3 in lung tissue showed no significant differences between C and S groups （P 〉 0 .05） .In IR 6h group ,IL‐6 mRNA expres‐sion markedly increased ,peaked in IR48h group and returned to baseline in IR5d group .In IR48h group ,the expression level of MKK3 mRNA was markedly higher than those in IR24h and IR6h groups （ P 〈 0 .05） .And the values were markedly higher in IR24h and IR6h groups than that in IR5d group （ P 〈 0 .05） .[Conclusion] In murine model of ische‐mia‐reperfusion renal injury ,the expression of IL‐6 and TNF‐α are closely correlated with the degree of lung injury .It suggests that IL‐6 and TNF‐α are detrimental factors for acute lung injury .Kidney ischemia‐reperfusion may induce pul‐monary injury via p38 MAPK signaling pathway .