赖雁威,刘丽娟,黄艳平,武敬
LAI Yanwei,LIU Lijuan,HUANG Yanping,WU Jing

• 1:北京大学深圳医院药学部
• 2:罗湖区人民医院药学部

摘要(Abstract)：

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 m L/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TLR4、NF-κB m RNA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TLR4、NF-κB m RNA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TLR4、NF-κB m RNA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 m L/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 m RNA 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 m RNA 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 m RNA 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.

关键词(KeyWords)： 腹泻;大鼠,wistar;肠黏膜;大蒜素;Toll样受体4;核因子-κB
diarrhea;rats,wistar;intestinal mucosal;allicin;toll-like receptor 4(TLR4);nuclear factor-κB(NF-κB)

Abstract:

Keywords:

基金项目(Foundation): 深圳市科技创新委员会基金[深科技创新(2014)109号]

作者(Author): 赖雁威,刘丽娟,黄艳平,武敬
LAI Yanwei,LIU Lijuan,HUANG Yanping,WU Jing

DOI: 10.19367/j.cnki.2096-8388.2020.12.012

参考文献(References)：

• [1]刘凯杰，王红．慢性腹泻的诊断和治疗[J]．中华全科医师杂志，2018,17(10):770-773.
• [2]翁国武，刘真义．奥替溴胺联合洛哌丁胺治疗腹泻型肠易激综合征的疗效及机制分析[J]．安徽医药，2017,21(1):143-146.
• [3]王筱颖，许波，许伟，等．健脾八珍糕联合蒙脱石散治疗脾虚型小儿腹泻的效果及对免疫功能的改善情况[J]．中国妇幼保健，2020,35(5):877-880.
• [4]SHEN N,CHENG A L,QIU M G,et al. Allicin improves lung injury induced by sepsis via regulation of the toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MYD88)/nuclear factor kappa B(NF-κB)pathway[J]. Med Sci Monit,2019,25:2567-2576.
• [5]乔蕾，武秋林，孔春艳，等．大蒜素后处理对大鼠心肌缺血-再灌注损伤的影响[J]．郑州大学学报(医学版)，2018,53(5):595-598.
• [6]刘舒，高媛，肖露，等．两种慢性渗透性腹泻大鼠模型建立方法的比较[J]．中国病理生理杂志，2016,32(8):1484-1491.
• [7]石祖胶，姜溪，陈芙蓉，等．小儿止泻膏对幼龄大鼠慢性腹泻的治疗作用及机制研究[J]．药物评价研究，2017,40(4):496-499.
• [8]杨镛，蔡枫，徐燕丰，等．温补肾阳法影响慢性腹泻大鼠模型结肠AQP8表达和c AMP/c GMP比值的实验研究[J]．临床和实验医学杂志，2017,16(5):433-438.
• [9]赵义红，王菲，娄静．小檗碱对腹泻型肠易激综合征大鼠肠屏障功能、炎症反应及NF-kB p65的影响[J]．华西药学杂志，2019,34(6):592-596.
• [10]刘童蕾，曾玉剑，田衍，等．腹腔间隔室综合征大鼠血清D-乳酸及二胺氧化酶的变化及意义[J]．国际外科学杂志，2016,43(1):23-25.
• [11]何锐，朱烨柯，滕文彬，等．甘油可能通过水通道蛋白3减轻脓毒症小鼠肠黏膜屏障损伤[J]．基础医学与临床，2020,40(5):655-661.
• [12]GANESALINGAM K,ISMAIL S,CRAIG J P,et al. Use of a purpose-built impression cytology device for gene expression quantification at the ocular surface using quantitative PCR and droplet digital PCR[J]. Cornea,2019,38(1):127-133.
• [13]THANH H D T,THI H D,THANH T N,et al. Epidemiology of acute diarrhea caused by rotavirus in sentinel surveillance sites of Vietnam,2012-2015[J]. Vaccine,2018,36(51):7894-7900.
• [14]LANGA J S,THOMPSON R,ARNALDO P,et al. Epidemiology of rotavirus A diarrhea in chókwè，southern mozambique,from february to september,2011[J]. J Med Virol,2016,88(10):1751-1758.
• [15]GASPARINHO C,MIRANTE M C,SNIA C L,et al.Etiology of diarrhea in children younger than 5 years attending the bengo general hospital in angola[J]. Pediatr Infect Dis J,2016,35(2):28-34.
• [16]KUMAR P A,SALMIAH I,ZEINAB S,et al. Allicin alleviates dextran sodium sulfate-(DSS-)induced ulcerative colitis in BALB/c mice[J]. Oxid Med Cell Longev,2015,2015:605208.
• [17]蓝景生，张震，罗薇，等．大蒜素对心肌纤维化的影响及对TLR4/NF-κB信号通路的作用[J]．中国免疫学杂志，2016,32(4):500-503.
• [18]邵佳月，孙秀威．大蒜素联合5-FU对结肠癌HT-29细胞凋亡的影响及机制[J]．实用肿瘤学杂志，2018,32(4):289-292.
• [19]王先坤，王雪，黄建．大蒜素对大鼠实验性大肠癌的作用及其机制研究[J]．天然产物研究与开发，2016,28(6):943-948.
• [20]陶庆霞，张鹏，吴翠莹，等．大蒜素抗肿瘤作用及其机制的研究进展[J]．中华神经创伤外科电子杂志，2016,2(6):365-368.
• [21]李学文，郭为钧．大蒜素通过AKT/NF-κB通路诱导大肠癌细胞凋亡的实验研究[J]．现代消化及介入诊疗，2020,25(2):193-198.

文章评论(Comment)：