大蒜素通过TLR4/NF-κB途径对慢性腹泻大鼠肠黏膜修复和炎性因子的调节作用

The Role of Allicin in Regulating Intestinal Mucosal Repair and Inflammatory Factors via TLR4/NF-κB Pathway in Rats with Chronic Diarrhea

目的:探究大蒜素通过Toll样受体4(TLR4)/核因子-κB(NF-κB)对慢性腹泻大鼠肠黏膜修复及炎症因子的调节作用。方法:40只健康雄性Wistar大鼠均分为空白组、模型组、蒙脱石散组及大蒜素组,后3组大鼠建立慢性腹泻大鼠模型,模型复制成功后蒙脱石散组予1.0 g/kg蒙脱石散药液灌胃,大蒜素组予30 mg/kg大蒜素注射液灌胃治疗,空白组及模型组则给予15 mL/kg生理盐水灌胃,1次/d;治疗1周时,比较各组大鼠腹泻指数、腹泻率、稀便率、稀便等级、小肠含水量,血清D-乳酸、D-木糖水平及炎症因子白介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)含量,能量代谢因子琥珀酸脱氢酶(SDH)及淀粉酶活性,同时取肠黏膜组织检测TLR 4、NF-κB mRNA表达水平,并观察肠黏膜组织学改变。结果:治疗1周时,模型组、蒙脱石散组及大蒜素组大鼠的稀便率、稀便等级、腹泻指数及腹泻率,血清IL-1β、IL-6、TNF-α、PGE2含量,肠黏膜水肿、炎细胞浸润、溃疡、上皮损伤评分,肠黏膜组织TLR 4、NF-κB mRNA表达水平均高于空白组,绒毛高度、绒毛表面积低于空白组(P<0.05);蒙脱石散组及大蒜素组大鼠的D-木糖水平,SDH、淀粉酶活性、绒毛高度、绒毛表面积高于模型组,稀便率、稀便等级、腹泻指数及腹泻率、血清D-乳酸IL-1β、IL-6、TNF-α、PGE2,肠黏膜水肿、炎细胞浸润、溃疡、上皮损伤评分,肠黏膜组织TLR 4、NF-κB mRNA表达水平低于模型组(P<0.05)。结论:大蒜素可能通过干扰TLR4/NF-κB信号转导,抑制下游NF-κB活化,降低炎症因子表达,减轻慢性腹泻肠黏膜炎症反应,促进肠黏膜能量代谢、酶活性恢复,进而改善腹泻症状。

Objective:To investigate the role of allicin in regulating intestinal mucosal repair and inflammatory factors via Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)in rats with chronic diarrhea.Methods:Forty healthy male wistar rats were divided into blank,model,montmorillonite powder and allicin groups.Rats in the last three groups were established with chronic diarrhea models.After the model was successfully generated,montmorillonite powder group was given 1.0 g/kg montmorillonite powder by gavage,while allicin group was given 30 mg/kg allicin injection by gavage.The blank group and model group were given 15 mL/kg normal saline by gavage.The treatment was a once-daily for one week.We compared the diarrhea index,diarrhea rate,loose stool rate,loose stool grade,water content of small intestinal,the levels of serum D-lactic acid,D-xylose,inflammatory factor interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and prostaglandin E2(PGE2),the activities of energy metabolism factors such as succinate dehydrogenase(SDH)and amylase.In addition,TLR4 and NF-κB mRNA expression levels in intestinal mucosal tissue were measured.The histological changes of intestinal mucosa were observed.Results:After the treatment,the loose stool rate,loose stool grade,diarrhea index and diarrhea rate,serum IL-1β,IL-6,TNF-α,PGE2,intestinal mucosal edema,inflammatory cell infiltration,ulcer,epithelial injury scores,TLR4,NF-κB mRNA expression levels in intestinal mucosal tissue were higher in model,montmorillonite powder and allicin groups than those in the blank group,in contrast,villus height,villus surface area were lower in these three groups than those in the blank group(P<0.05).D-xylose levels,the activities of SDH and amylase,villus height and villus surface area were higher in montmorillonite and allicin groups than those in the model group,but the rate of loose stool,the grade of loose stool,the diarrhea index and the rate of diarrhea,and the serum D-lactic acid IL-1β,IL-6,TNF-α,PGE2,intestinal mucosal edema,inflammatory cell infiltration,ulcer,epithelial injury score,TLR4,NF-κB mRNA expression levels in intestinal mucosal tissue were lower in montmorillonite and allicin groups than those in the model group(P<0.05).Conclusion:Allicin might interfere with TLR4/NF-κB signal transduction,inhibit NF-κB activation,reduce the expression levels of inflammatory factors,decrease intestinal mucosal inflammation of chronic diarrhea,promote intestinal mucosal energy metabolism and recover enzyme activity,thus relieving diarrhea symptoms.