NF-κB、IL-6和TNF-α在抗IL-6受体单抗干预早期急性肺损伤大鼠肺组织中的表达

Effect of Anti-rat IL-6R Monoclonal Antibody on Expression of IL-6、TNF-α、NF-κB in Acute Lung Injury Rats in the Early Stage

目的观察NF-κB、IL-6、TNF-α在抗IL-6R单抗干预急性肺损伤(ALI)早期大鼠肺组织中的表达,探讨抗IL-6受体单抗(抗IL-6R单抗)保护肺组织的作用机制。方法40只大鼠随机分成5组:ALI组,抗IL-6R单抗干预组,兔IgG干预组,地塞米松干预组,生理盐水对照组,每组8只。先给予脂多糖(LPS)总剂量(8mg/kg)的1/10腹腔注射,12h后再给予余量,制备大鼠ALI模型。抗IL-6R单抗、兔IgG、地塞米松的剂量分别为200μg/kg、200μg/kg和2mg/kg。采用免疫组化技术观察各组动物肺组织中NF-κB、IL-6和TNF-α在干预因素作用下的早期ALI大鼠肺组织中的表达。结果与对照组比较,抗IL-6R单抗均能抑制ALI肺组织中NF-κB、IL-6的表达,而TNF-α的表达未见下调。结论抗IL-6R单抗使ALI大鼠肺组织中NF-κB的表达下降,可能为抗IL-6R单抗对ALI有保护作用的机制之一。

Objective To observe the changes of IL-6,TNF-α,NF-KB in lungs of rats interferd with Anti-rat IL-6R monoclonal antibody in acute lung injury （ALl）in the early stage, and try to find the potential mechanisms of the protective effects of anti-rat IL-6R monoclonal antibody on ALI. Meth- ods Forty SD Rats were randomly divided into 5 groups, with 8 rats in each group. The control group was given normal saline （0 9ml/kg） lml intra-peritoneally （IP）; ALI group was induced by LPS（Smg/kg BW） given IP with 1/10 LPS before the experiment and in the rest LPS and normal saline were given 12h later. For dexamethasone interference group, anti-rat IL-6R monoclonal antibody interference group and rabbit IgG interference group, the rats received dexamethasone （2mg/kg BW ）, Anti-rat IL-6R mono- clonal antibody（200μg/kg） and rabbit IgG （200μg/kg） IP respectively, while LPS was administered on the second time. Comparison of pathological change was made with light microscope and the change of expression of IL-6, TNF-α and NF-KB was monitored in immunohistochemical method. Results Anti- IL-6R monoclonal antibody was able to down-regulate NF-KB and IL-6 expression in ALl lung tissue, while it seemed not to affect the TNF-α expression in ALI lung tissue. Conclusion The down-regula- tion of NF-KB in lung tissue may be one of causes of protective effect after the administration of anti-rat IL-6R monoclonal antibody in ALI rats.