吴茱萸碱对结肠炎大鼠炎性树突状细胞的调控作用

Effect of Evodiamine on Inflammatory Dendritic Cells in Colitis Rats

目的探讨吴茱萸碱(Evodiamine,Evo)对溃疡性结肠炎(Ulcerative colitis,UC)大鼠炎性树突状细胞(Inflammatory dendritic cells,infDCs)的调控作用。方法将SD大鼠随机分为6组,即正常组、模型组、Evo高剂量组(40 mg·kg^-1)、Evo中剂量组(20 mg·kg^-1)、Evo低剂量组(10 mg·kg^-1)及美沙拉嗪组(150 mg·kg^-1),每组8只。除正常组外其余各组采用三硝基苯磺酸(TNBS)-乙醇复合法进行造模。造模24 h后按照相应剂量灌胃给药,连续给药7 d。给药结束后,称定大鼠体质量,处死并分离结肠组织,测量长度,称定质量,计算结肠质量指数;采用HE染色进行结肠组织病理学观察;分离派氏淋巴结和肠系膜淋巴结,采用流式细胞术检测CD11c^+CD103^+E-cadherin+T细胞数量;ELISA法测定大鼠结肠组织匀浆中干扰素-γ(IFN-γ)、细胞间黏附分子-1(ICAM-1)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)及白细胞介素-2(IL-2)水平。结果与正常组比较,模型组大鼠的体质量及结肠长度均明显降低或缩短(P<0.01),结肠质量、结肠质量指数明显升高(P<0.05,P<0.01);结肠组织CD11c^+CD103^+E-cadherin+T细胞数量显著增加(P<0.01);IL-6、ICAM-1水平明显升高(P<0.05),IFN-γ水平明显降低(P<0.05)。与模型组比较,各给药组的结肠质量、结肠质量指数均明显降低(P<0.05),Evo高剂量组的大鼠体质量明显升高(P<0.05),Evo高、低剂量组的大鼠结肠长度明显增加(P<0.05);各给药组的大鼠结肠组织CD11c^+CD103^+E-cadherin+T细胞数量显著降低(P<0.05,P<0.01),IL-10水平明显升高(P<0.05,P<0.01),ICAM-1、IL-2明显降低(P<0.05,P<0.01);Evo高、中剂量组的IL-6明显降低(P<0.05,P<0.01);Evo中、低剂量组的IFN-γ水平明显升高(P<0.05,P<0.01)。结论吴茱萸碱可能通过降低infDCs细胞数量,下调IL-2、ICAM-1、IL-6表达,上调IL-10、IFN-γ表达,从而发挥治疗UC的作用。

Objective To investigate the effect of Evodiamine(Evo) on the regulation of inflammatory dendritic cells(InfDCs) in ulcerative colitis(UC) rats.Methods SD rats were randomly divided into 6 groups:normal group,model group,Evo high dose group(40 mg·kg^-1),Evo medium dose group(20 mg·kg^-1),Evo low dose group(10 mg·kg^-1),and mesalazine group(150 mg·kg^-1),8 in each group.Except the normal group,the other groups were modeled by trinitrobenzenesulfonic acid(TNBS)-ethanol composite method.After modeling for 24 h,rats were intragastrically administered the corresponding doses of drugs for 7 days.After the last administration,the body mass of the rats was weighed.The rats were sacrificed,the length of colon tissue separated was measured,and the mass was weighed for calculation of the colon mass index.Histopathological observation of colon tissue was performed by HE staining.The number of CD11c^+CD103^+E-cadherin+T cells was detected by flow cytometry.Determination of IFN-γ,ICAM-1,IL-6,IL-10 and IL-2 levels in rat colon homogenate were carried out by ELISA.Results Compared with the normal group,the body weight and colon length of the model group rats were significantly reduced or shortened(P<0.01);colon mass and colon mass index were significantly increased(P<0.05,P<0.01);the number of CD11c^+CD103^+E-cadherin+T cells in colon tissue increased significantly(P<0.01);IL-6 and ICAM-1 levels were significantly increased(P<0.05),and IFN-γ level was significantly decreased(P<0.05).Compared with the model group,the colon mass and colon mass index of each drug-administered group were significantly lower(P<0.05),and the body mass of the Evo high-dose group was significantly higher(P<0.05),the colon length of Evo high and low dose groups increased significantly(P<0.05);the numbers of CD11c^+CD103^+E-cadherin+T cells in the colon tissue of each drug-administered group were significantly decreased(P<0.05,P<0.01),and the levels of IL-10 were significantly increased(P<0.05,P<0.01),ICAM-1,IL-2 decreased significantly(P<0.05,P<0.01);IL-6 in Evo high and medium dose groups decreased significantly(P<0.05,P<0.01);IFN-γ levels in Evo medium and low dose groups were significantly increased(P<0.05,P<0.01).Conclusion Evo can reduce the expression of IL-2,ICAM-1,IL-6,up-regulate the expression of IL-10 and IFN-γ by decreasing the number of infDCs,thereby exert the effect of treating UC.