艾灸通过调控NLRP3炎性小体缓解5-氟尿嘧啶诱导的大鼠化疗性肠黏膜炎的实验研究

Experimental Study on Moxibustion to Relieve 5-Fluorouracil-Induced Chemointestinal Mucositis in Rats by Regulating NLRP3 Inflammatory Body

目的:探讨艾灸通过调控核苷酸结合寡聚化结构域样受体3(NLRP3)缓解5-氟尿嘧啶(5-FU)诱导的化疗性肠黏膜炎的作用机制。方法:将30只SD大鼠随机分为正常组、模型组和艾灸组,每组10只,造模前7 d对艾灸组行艾灸处理,模型组与艾灸组采用单次腹腔注射5-FU造模,造模完成后,艾灸组继续行艾灸处理,正常组与模型组常规饲养,观察各组大鼠一般情况,检测血清中IL-1β、TNF-α、NLRP3含量,观察结肠组织病理改变,检测结肠组织NLRP3 mRNA表达水平,以及NLRP3组成相关蛋白及IL-1β的表达。结果:腹腔注射5-FU后,模型组体质量和摄食量下降明显,肠黏膜形态不规则,损伤严重,肠绒毛变短融合,上皮细胞排列紊乱。与模型组比较,艾灸组体质量增长、血便、摄食量均有不同程度改善,疾病活动指数评分显著低于模型组。艾灸组血清中IL-1β、TNF-α、NLRP3含量均显著低于模型组(P<0.05或P<0.01);艾灸组结肠组织中NLRP3炎性小体组成部分NLRP3、Caspase-1、ASC蛋白及IL-1β表达显著低于模型组(P<0.05)。结论:艾灸可通过抑制NLRP3炎性小体改善5-FU诱导的大鼠化疗性肠黏膜炎症状。

Objective:To explore the mechanism of moxibustion to relieve 5-fluorouracil(5-FU)-induced chemotherapy intestinal mucositis by regulating NLRP3 inflammatory body.Methods:A total of 30 SD rats were randomly divided into normal group,model group and moxibustion group,10 rats in each group.The moxibustion group was treated with moxibustion 7 days before the model was made.The model group and the moxibustion group were injected with a single intraperitoneal injection of 5-FU.After the model building was completed,the moxibustion group continued to be treated with moxibustion,the normal group and the model group were fed regularly.The general situation,the expression of IL-1β,TNF-α,NLRP3 in serum,pathological changes of colon tissue;the expression of NLRP3 mRNA in colon tissue and the expression levels of NLRP3,Caspase,ASC,IL-1βprotein in colon were observed.Results:After intraperitoneal injection of 5-FU,the body weight and food intake of the model group decreased significantly,the morphology of intestinal mucosa was irregular,the injury was serious,intestinal villi shortened and fused,and the epithelial cells were disordered.Compared with the model group,the body mass growth,blood stool,and food intake of the moxibustion group were improved to varying degrees,and the disease activity index score was significantly lower than the model group.The content of IL-1β,TNF-αand NLRP3 in serum of moxibustion group were significantly lower than that of model group(P<0.05 or P<0.01).The expressions of NLRP3,Caspase-1,ASC protein and IL-1βin NLRP3 inflammatory body in colon tissue of moxibustion group were significantly lower than those in the model group(P<0.05).Conclusion:Moxibustion can improve 5-FU-induced intestinal mucosal inflammation in rats by inhibiting NLRP3 inflammatory bodies.