益生菌联合美沙拉嗪治疗小鼠溃疡性结肠炎的效果及机制

目的观察嗜酸乳杆菌联合美沙拉嗪对小鼠溃疡性结肠炎（UC）的治疗作用,并探讨其可能的作用机制。方法 2.5%DSS 7d建立急性UC动物模型。将70只BALB/c小鼠随机分为7组：分别为正常组、模型组、阴性对照（生理盐水,NS）组、美沙拉嗪组、嗜酸乳杆菌低剂量组（106CFU/ml）、嗜酸乳杆菌高剂量组（108CFU/ml）、嗜酸乳杆菌联合美沙拉嗪组,观察指标包括：疾病活动指数（DAI）、结肠粘膜肉眼改变及病理组织学积分;采用免疫组化SABC法检测热休克蛋白70（HSP70）和c-Jun氨基末端激酶（JNK）的表达量;结果嗜酸乳杆菌可降低实验小鼠DAI积分和改善结肠组织损伤;与模型组、阴性对照组相比,嗜酸乳杆菌低、高剂量组、嗜酸乳杆菌联合美沙拉嗪组JNK蛋白的表达下降（P〈0.05）,HSP70的表达增加（P〈0.05）,其中以嗜酸乳杆菌联合美沙拉嗪组效果最佳。结论嗜酸乳杆菌和美沙拉嗪对小鼠溃疡性结肠炎都有治疗作用,且二者疗效相当;两药联合应用效果最佳。其机制可能与抑制JNK的激活、增加结肠粘膜HSP70的表达有关。

The effect of probiotics and mesalazine on ulcerative colitis in mice and their potential mechanisms

Objective To investigate the effect of probiotics-lactobacillus Combined with mesalazine on ulcerative colitis in mice to find its possible mechanism of treating UC.Methods Experimental colitis was induced by drinking 2.5% dextran sulfate sodium（DSS） freely for 7 consecutive days.Seventy mice were randomly divided into seven groups as follows： normal control group,model control group,negative control group（normal saline,NS）,mesalazine group,low-dose（106CFU/ml）,high-dose（108CFU/ml） lactobacillus acidophilus group and lactobacillus acidophilus combined with mesalazine group.Disease activity index（DAI） and histological injury scores were used to assess the efficacy of intervention groups;HSP70 and JNK expression in colonic mucosa were measured by immunohistochemistry（IHC）.Results Probiotics could significantly reduce the DAI and colonic histological scores of experimental mice;The expression of JNK at protein level was decreased（P 〈0.05） in low-dose,high-dose lactobacillus acidophilus group and lactobacillus acidophilus Combined with mesalazine group,compared with model control and negative control groups;The expression of HSP70 was increased.which was most evidenced in lactobacillus acidophilus Combined with mesalazine group.Conclusion Both Lactobacillus acidophilus and mesalazine were effective on trearment of UC.Efficiency of Lactobacillus acidophilus is similar to that of mesalazine.lactobacillus acidophilus Combined with mesalazine is the best.Its mechanism may be related to the inhibition of the activation of JNK and up-regulation of HSP70.