VX-680对小鼠实验性结肠炎NF-κB通路的调节作用

Effects of VX-680 on the regulation of NF-κB pathway in experimental colitis in mice

目的探究极光激酶A(Aurora-A)抑制剂(VX-680)对小鼠实验性结肠炎的作用以及对NF-κB通路的调节作用。方法选择18只体质量相近的C57BL/6小鼠,随机分为3组,每组各6只:对照组(正常饮水+10%DMSO溶剂腹腔注射7 d)、DSS模型组(3%DSS饮水造模+10%DMSO溶剂腹腔注射7 d)、治疗组[3%DSS饮水造模+VX-680(40 mg/kg)腹腔注射7 d]。记录小鼠肠炎疾病活动指数(disease activity index,DAI)和结肠组织病理评分,ELISA检测小鼠结肠组织炎性因子IL-1β、IL-6、IL-10、TNF-α、IFN-γ的变化,qRT-PCR检测Mucin-1、Mucin-2、NF-κB p65的mRNA表达,检测Aurora-A和NF-κB通路中NF-κB p65、IRF-5的蛋白表达。结果与对照组相比,DSS模型组DAI评分和组织病理学评分更高(P<0.01),促炎因子IL-1β、IL-6、TNF-α、IFN-γ的表达上升(P<0.01),Mucin-1、Mucin-2的mRNA水平下降(P<0.01),NF-κB p65、IRF-5的表达水平上升(P<0.01);治疗组对上述改变有缓解作用(P<0.01)。结论VX-680可通过NF-κB通路抑制肠道炎症,保护肠道黏膜。

Objective To investigate the effect of Aurora-A inhibitor(VX-680)on experimental colitis in mice and the regulation of NF-κB pathway.Methods Eighteen C57BL/6 mice of similar body weight were selected and randomly divided into three groups of six mice each:control group(normal drinking water+10%DMSO solvent intraperitoneally for 7 days),DSS model group(3%DSS drinking water modeling+10%DMSO solvent intraperitoneally for 7 days),and treatment group[3%DSS drinking water modeling+VX-680(40 mg/kg)intraperitoneally for 7 days].The disease activity index(DAI)and colon histopathology score of mice with enteritis were recorded,and the changes of inflammatory factors IL-1β,IL-6,IL-10,TNF-αand IFN-γin mice colon tissue were detected by ELISA.mRNA expression of Mucin-1,Mucin-2 and NF-κB p65 was detected by qRT-PCR,Aurora-A and NF-κB p65,IRF-5 protein expression in NF-κB pathway was detected.Results Compared with the control group,the DSS model group had higher DAI score and histopathology score(P<0.01),and the expression of pro-inflammatory factors IL-1β,IL-6,TNF-α,and IFN-γwas increased(P<0.01),Mucin-1 and Mucin-2 mRNA levels were decreased(P<0.01),and expression level of NF-κB p65 and IRF-5 was increased(P<0.01);the treatment group had a mitigating effect on the above changes(P<0.01).Conclusion VX-680 can inhibit intestinal inflammation and protect intestinal mucosa through NF-κB pathway.