美沙拉嗪通过抑制经典炎性信号通路激活治疗噁唑酮诱导的小鼠结肠炎中炎症反应

目的：探究美沙拉嗪在噁唑酮诱导的小鼠溃疡性结肠炎模型中的治疗作用与机制。方法：60只小鼠随机分为对照组、模型组、低剂量给药组和高剂量给药组,所有小鼠按照相同方式先后进行2次致敏。致敏5 d后麻醉小鼠,对照组小鼠按0.15 ml/g体重灌肠50%乙醇水溶液,灌注后倒置小鼠30 s,其余各组小鼠按相等剂量灌肠1%噁唑酮乙醇（50%）溶液。给药组按体重不同分别给予不同剂量的美沙拉嗪灌胃,对照组和模型组给予相同体积的溶剂灌胃。结果：噁唑酮造模后小鼠体重明显下降,给药组较模型组体重有所恢复;模型组小鼠肠道结构损伤严重,给药后炎症和损伤程度有所缓解;模型组小鼠血清中Th2型细胞因子含量显著增多（P<0.05）,美沙拉嗪能够缓解炎症因子的大量释放,同时模型小鼠结肠组织NF-κB信号通路关键蛋白p-p65、p-IκB蛋白的表达显著增加,同时p65、IκB蛋白的降低,给药后蛋白水平恢复。结论：美沙拉嗪能够有效地恢复噁唑酮引起的小鼠体重下降和结肠组织炎性细胞浸润,同时能够保护噁唑酮引起的结肠组织损伤,美沙拉嗪同时对于噁唑酮诱导的Th2型细胞因子释放具有显著的抑制作用,可以通过抑制NF-κB通路的激活,从而经经典炎症通路发挥抗炎作用。

Mesalazine inhibits inflammatory response in mice with colitis by inhibiting activation of classical inflammatory signaling pathways

Objective: To investigate the therapeutic effect and mechanism of mesalazine in oxazolone-induced mouse model of ulcerative colitis. Methods:60 mice were randomly divided into control group, model group and low dose group and high dose group. All mice were sensitized two times successively in the same way. After 5 days of sensitization, the mice in the control group were clystered with 50% ethanol water solution with 0.15 ml/g body weight, and the mice were inverted 30s after perfusion.The remaining mice in each group were clystered with 1% oxazolone-ethanol (50%) solution at the same dose.The mice in the treatment group were given different doses of mesalazine orally according to their weight, and the control group and the model group were given the same volume of solvent to fill the stomach. Results: After oxazolone modeling, the body weight of the mice decreased significantly.The weight of the drug-treated group was restored compared with the model group.The intestinal structure of the model group was severely damaged, and the degree of inflammation and injury was relieved after administration. The content of Th2 type cytokines in the serum of model group was significantly increased (P<0.05). Mesalazine can alleviate the massive release of inflammatory factors. At the same time, the expression of p-p65 and p-IκB proteins in the NF-κB signaling pathway of the colon tissue of the model mice increased significantly, while the p65 and IκB proteins decreased, and the protein level recovered after administration. Conclusion: Mesalazine can effectively restore oxazolone-induced weight loss in mice and inflammatory cell infiltration in the colon, while protecting oxazolone-induced colon tissue injury. Mesalazine also has a significant inhibitory effect on oxazolone-induced Th2 type cytokine release, and can exert anti-inflammatory effects by inhibiting the activation of the NF-κB pathway.