摘要
目的 研究抗IL-20 单抗在金黄色葡萄球菌(staphylococcus aureus,SA)肺炎中的作用.方法 小鼠随机分为对照组、模型组、抗IL-20 单抗 7E干预组(7E)和万古霉素阳性对照组(Vanc).通过气管滴注法建立小鼠SA肺炎小鼠模型,干预组在造模后通过尾静脉注射给药.收集外周血,并对外周血中白细胞和中性粒细胞计数,ELISA法检测血清中CRP、IL-20、TNF-α、IL-6和IL-1β水平;HE染色观察肺组织病理形态变化(包括肺泡结构完整性、肺泡间隔厚度、炎症、坏死及炎性细胞浸润情况),免疫组织化学和Western blot检测小鼠肺组织中TLR2、NF-κB p65、p-STAT3的表达.结果 与对照组比较,模型组肺发生明显病理改变,而 7E组和Vanc组肺组织病理形态明显改善,治疗第 3 天开始肺泡恢复,无明显炎性细胞浸润.治疗后第4 d,7E组和Vanc组外周血中白细胞和中性粒细胞计数、血清中IL-20、TNF-α、IL-6 和IL-1β含量以及肺组织中TLR2、NF-κB p65、p-STAT3的表达均明显降低.结论 抗IL-20单抗7E可能通过抗炎作用延缓SA的进展,其机制可能与抑制STAT3以及TLR2/NF-κB通路有关.
Abstract
Objective To study the role of anti-IL-20 monoclonal antibody in staphylococcus aureus(SA)pneumonia.Meth-ods Mice were randomly divided into control group,model group,anti-IL-20 monoclonal antibody 7E intervention group(7E),and vancomycin positive control group(Vanc).A mouse model of SA pneumonia was established by tracheal instillation.The intervention group was administered medication via tail vein injection after modeling.Peripheral blood was collected,and white blood cell and neutrophil counts were measured in peripheral blood,serum levels of CRP,IL-20,TNF-α,IL-6,and IL-1β were detected by ELISA;HE staining observed the pathological morphological changes in lung tissue(including the integrity of alveolar structure,thickness of alveolar septa,inflammation,necrosis,and inflammatory cell infiltration),immunohistochemistry and Western blot were used to detect the expression of TLR2,NF-κB p65,and p-STAT3 in mouse lung tissue.Results Compared with the control group,the model group showed significant pathological changes in the lungs,while the 7E group and Vanc group showed significant improvement in lung tissue morphology,with alveoli beginning to recover from day 3 of treatment,with no significant inflammatory cell infiltration.On day 4 after treatment,the counts of white blood cells and neutrophils in peripheral blood,the levels of IL-20,TNF-α,IL-6,and IL-1β in serum,and the expression of TLR2,NF-κB p65,and p-STAT3 in lung tissue were significantly reduced in both the 7E and Vanc groups.Conclusion The anti-IL-20 monoclonal antibody 7E may delay the progression of SA through its anti-inflammatory effects,which may be related to the inhibition of the STAT3 and TLR2/NF-κB pathways.