半夏泻心汤对氟尿嘧啶致腹泻小鼠模型肠道免疫功能的影响

Effects of Banxia Xiexin Tang on Intestinal Immune Function in Fluorouracil-induced Diarrhea Mice

摘要:

目的: 研究半夏泻心汤对氟尿嘧啶致腹泻小鼠模型肠道免疫功能的影响,揭示其治疗化疗相关性腹泻的作用机制. 方法: 采用腹腔注射氟尿嘧啶(40 mg·kg^-1)连续6 d,建立小鼠腹泻模型.随机分为6组:正常组,模型组,阳性药组(蒙脱石散1.17 g·kg^-1),半夏泻心汤高、中、低剂量组(2.5,1.25,0.625 g·kg^-1),造模前给药2 d,连续给药11 d.观察小鼠每日活动状况、进食量、体重、腹泻变化情况,检测胸腺、脾脏质量,取回肠组织做病理切片,采用ELISA法测定小肠中免疫球蛋白A(IgA)、血管活性肠肽(VIP)、白细胞介素15(IL-15)的含量. 结果: 与正常组比较,模型组小鼠化疗后腹泻加重,体重、胸腺及脾脏指数减小,肠道IgA,VIP的含量降低,而IL-15含量升高;与模型组比较,半夏泻心汤各剂量组能显著抑制氟尿嘧啶造成的小鼠体重降低、胸腺、脾脏指数减小,降低腹泻发生率,同时增加肠道IgA,VIP的含量,减少IL-15的含量(P<0.05或P<0.01). 结论: 半夏泻心汤能治疗化疗相关性腹泻,可能与其调节肠黏膜免疫功能有关.

Abstract:

Objective: To study the effect of Banxia Xiexin Tang on intestinal immune function in fluorouracil-induced diarrhea mice, and to reveal the therapeutic mechanism on chemotherapy-induced diarrhea. Method: The fluorouracil(40 mg· kg^-1) was intraperitoneal injected for 6 days to establish the diarrhea mice model. Sixty ICR mice were randomized into 6 groups:normal group, model group,montmorillonite powder group(1.17 g·kg^-1), Banxia Xiexin Tang(2.5,1.25,0.625 g· kg^-1) group, administrated by oral gavage for 2 day before modeling, the intervention period lasted 11 days. Then we observed the changes of daily activity status, food intake, body weight, diarrhea, measured the quality of the thymus and spleen, observed the pathological changes of ileal tissue, measured the expression of intestinal immunoglobulin A (IgA), vasoactive intestinal peptide (VIP), interleukin-15(IL-15)by ELISA method. Result: Compared to normal group, the diarrhea of model group mice was aggravated and the weight, thymus and spleen index were decreased, the levels of IgA and VIP were decreased, whereas the IL-15 was increased.Compared to model group,Banxia Xiexin Tang could significantly inhibit body weight loss, diarrhea and spleen, thymus reduction induced by fluorouracil in mice. Banxia Xiexin Tang could increase the levels of IgA and VIP and decrease IL-15 expression (P<0.05, P<0.01). Conclusion: Banxia Xiexin Tang could prevent the fluorouracil induced diarrhea by up-regulating the expression of IgA, VIP and down-regulating the expression of IL-15, thereby generating immune protection.