羌活醇对葡聚糖硫酸钠诱导的结肠炎小鼠作用的研究

Study on Effect of Notopterol on Dextran Sulfate Sodium-induced Colitis in Mice

背景:免疫功能失调在炎症性肠病(IBD)的发病机制中起着关键作用。羌活醇是中药羌活的主要活性成分,具有抗炎的作用。目的:探究羌活醇对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎的作用。方法:将C57BL/6小鼠随机分为正常组、阴性对照组、模型组、羌活醇组。模型组、羌活醇组小鼠自由饮用2%DSS溶液诱导结肠炎模型。阴性对照组、羌活醇组小鼠给予腹腔注射羌活醇溶液40 mg/kg,正常组、模型组小鼠给予腹腔注射等体积0.9%NaCl溶液。10 d后处死小鼠,行疾病活动指数(DAI)评分、结肠长度和组织病理学评分,ELISA法检测结肠组织中TNF-α、IL-1β、IL-6、IL-17A水平,定量PCR法检测结肠和脾脏组织中IL-17A、RORγt mRNA表达。结果:与正常组相比,模型组DAI评分、组织病理学评分、结肠组织中TNF-α、IL-1β、IL-6、IL-17A水平、结肠和脾脏组织中IL-17A、RORγt mRNA表达均显著增高(P<0.01),结肠长度明显缩短(P<0.01)。与模型组相比,羌活醇能明显降低小鼠DAI评分、组织病理学评分(P<0.01),下调TNF-α、IL-1β、IL-6、IL-17A水平(P<0.01),抑制IL-17A、RORγt mRNA表达(P<0.01),明显恢复结肠长度(P<0.01)。结论:羌活醇对小鼠结肠炎有保护作用,其机制可能与减少促炎细胞因子的产生、抑制Th17细胞的功能和分化相关。

Background:Immunological dysfunction plays a key role in the pathogenesis of inflammatory bowel disease(IBD).Notopterol is the main ingredient of the traditional Chinese herb medicine Notopterygium incisum Ting ex H.T.Chang and has anti-inflammatory effect.Aims:To explore the effect of notopterol on dextran sulfate sodium(DSS)-induced colitis in mice.Methods:C57BL/6 mice were randomly divided into normal group,negative control group,model group and notopterol group.Mice in model group and notopterol group were treated with 2%DSS to induce colitis.Mice in negative control group and notopterol group were injected intraperitoneally with notopterol 40 mg/kg,and mice in normal group and model group were injected intraperitoneally with 0.9%NaCl solution.Mice were sacrificed 10 days later,and disease activity index(DAI)score,colon length and histopathological score were determined.The levels of TNF-α,IL-1β,IL-6,IL-17A were assessed by ELISA.The mRNA expressions of IL-17A,RORγt were detected by quantitative PCR.Results:Compared with the normal group,DAI score,histopathological score,levels of TNF-α,IL-1β,IL-6,IL-17A,mRNA expressions of IL-17A and RORγt in model group were significantly increased(P<0.01),and colon length were significantly shortened(P<0.01).Compared with the model group,notopterol significantly reduced DAI score and histopathological score(P<0.01),downregulated levels of TNF-α,IL-1β,IL-6,IL-17A(P<0.01),inhibited the mRNA expressions of IL-17A,RORγt(P<0.01),and greatly recovered colon length(P<0.01).Conclusions:Notopterol has protective effects on DSS-induced colitis in mice.The mechanism may be related to reducing the secretion of pro-inflammatory cytokines and inhibiting the function and differentiation of Th17 cells.