泻剂结肠是由于长期服用刺激类泻剂导致的肠神经受损,临床表现为顽固性便秘,目前缺乏有效的治疗手段。该研究通过灌胃番泻叶提取物建立小鼠泻剂结肠模型,分析两歧双歧杆菌FGSYC45M3缓解泻剂结肠小鼠便秘及修复其肠神经的效果,并探究其可能的作用机制。结果显示,两歧双歧杆菌FGSYC45M3能够显著缩短泻剂结肠小鼠的首粒黑便时间并提高粪便含水量。其作用机制可能与FGSYC45M3提高粪便中丁酸含量,恢复肠神经胶质细胞数量,提高胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)和乙酰胆碱酯酶(acetylcholinesterase,AChE)水平,增加结肠Cajal间质细胞(interstitial cells of Cajal,ICC)数量并降低水通道蛋白(aquaporins,AQPs)表达量相关。该研究提供了一种利用益生菌在缓解泻剂结肠患者便秘的基础上重建受损的肠神经系统,并建立正常的肠道稳态,以实现泻剂结肠缓解的思路,有望从根本上改善泻剂结肠。
[1] 张燕, 李红岩.泻剂引起结肠壁形态学改变的临床意义[J].中国临床解剖学杂志, 2004, 22(4):405-407;416.
ZHANG Y, LI H Y.The clinical significance of rhubarb causing the morphological changes in colon wall[J].Chinese Journal of Clinical Anatomy,2004,22(4):405-407;416.
[2] 徐毅, 王诗怡, 范一宏, 等.枳实水提物对大鼠泻剂结肠肠壁神经丛的影响及机制研究[J].中华中医药杂志, 2017, 32(2):761-766.
XU Y,WANG S Y,FAN Y H, et al.Effects and mechanism of aqueous extracts of Fructus Aurantii Immaturus (FAI) on intestinal plexus in cathartic colon of rats[J].China Journal of Traditional Chinese Medicine and Pharmacy, 2017, 32(2):761-766.
[3] JOO J S, EHRENPREIS E D, GONZALEZ L, et al.Alterations in colonic anatomy induced by chronic stimulant laxatives:The cathartic colon revisited [J].Journal of Clinical Gastroenterology, 1998, 26(4):283-286.
[4] 蓝海波,魏雨,甘华田, 等.《2017版便秘的分度与临床策略专家共识》解读[J].结直肠肛门外科,2020,26(3):257-259.
LAN H B, WEI Y, GAN H T, et al.Interpretation of 2017 edition expert consensus of severity and treatment strategy for constipation[J].Journal of Colorectal & Anal Surgery, 2020,26(3):257-259.
[5] NIESLER B, KUERTEN S, DEMIR I E, et al.Disorders of the enteric nervous system-A holistic view [J].Nature Reviews Gastroenterology & Hepatology, 2021,18(6):393-410.
[6] HEISS C N, OLOFSSON L E.The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system [J].Journal of Neuroendocrinology, 2019, 31(5):e12684.
[7] WANG L L, CHEN C L, CUI S M, et al.Adhesive bifidobacterium induced changes in cecal microbiome alleviated constipation in mice [J].Frontiers in Microbiology, 2019, 10:1 721.
[8] WANG L L, HU L, XU Q, et al.Bifidobacterium adolescentis exerts strain-specific effects on constipation induced by loperamide in BALB/c Mice [J].International Journal of Molecular Sciences, 2017, 18(2):318.
[9] IBARRA A, LATREILLE-BARBIER M, DONAZZOLO Y, et al.Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation:A double-blind, randomized, placebo-controlled, and dose-ranging trial [J].Gut Microbes, 2018, 9(3):236-251.
[10] 王琳琳. 双歧杆菌对便秘的影响及其作用机理研究[D].无锡:江南大学, 2017.
WANG L L, Study of the effects and mechanisms of bifidobacteria on constipation alleviation[D].Wuxi:Jiangnan University,2017.
[11] 王俊通. 产共轭亚油酸乳酸菌对DSS诱导小鼠结肠炎的改善作用 [D].无锡:江南大学, 2016.
WANG J T, Ameliorating effects of CLA-producing lactic acid bacteria on DSS-induced colitis in mice [D].Wuxi:Jiangnan University,2016.
[12] 毛丙永. 功能性低聚糖对肠道细菌的影响及机制 [D].无锡:江南大学, 2015.
MAO B Y, Effects of functional oligosaccharides on the gut bacteria and the mechanism [D].Wuxi:Jiangnan University,2015.
[13] BASSOTTI G, VILLANACCI V, MAURER C A, et al.The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation [J].Gut, 2006, 55(1):41-46.
[14] KABOURIDIS P S, LASRADO R, MCCALLUM S, et al.Microbiota controls the homeostasis of glial cells in the gut lamina propria [J].Neuron, 2015, 85(2):289-295.
[15] VERGNOLLE N, CIRILLO C.Neurons and glia in the rnteric nervous system and epithelial barrier function [J].Physiology, 2018, 33(4):269-280.
[16] MAHATO A K, KOPRA J, RENKO J M, et al.Glial cell line-derived neurotrophic factor receptor rearranged during transfection agonist supports dopamine neurons in vitro and enhances dopamine release in vivo [J].Movement Disorders, 2020, 35(2):245-255.
[17] WANG H, HUGHES I, PLANER W, et al.The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function [J].Journal of Neuroscience, 2010, 30(4):1 523-1 538.
[18] 陈颖颖. 抑制乙酰胆碱酯酶对视网膜炎症保护作用及机制的研究 [D].南昌:南昌大学, 2016.
CHEN Y Y.Protective effect and mechanism of inhibiting acetylcholinesterase on retinal inflammation [D].Nanchang:Nanchang University,2016
[19] PICKETT M A, DUSH M K, NASCONE-YODER N M.Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis [J].Development, 2017, 144(15):2 764-2 770.
[20] SPERLING L E, KLACZINSKI J, SCHÜETZ C, et al.Mouse acetylcholinesterase enhances neurite outgrowth of rat R28 cells through interaction with laminin-1 [J].PloS One, 2012, 7(5):e36683.
[21] 王琳琳, 王刚, 张灏, 等.具粘附特性的动物双歧杆菌对便秘模型小鼠血清中胃肠调节肽水平的影响 [J].中国食品学报, 2019, 19(6):13-20.
WANG L L,WANG G,ZHANG H, et al.The effect of bifidobacterium animalis with adhesive properties on the levels of gastrointestinal peptide neurotransmitter in serum of mice with constipation [J].Journal of Chinese Institute of Food Science and Technology,2019,19(6):13-20.
[22] 陈绪勇. 巨噬细胞活化对先天性巨结肠Cajal间质细胞及肠道电活动的影响 [D].武汉:华中科技大学, 2017.
CHEN X Y.The effects of macrophage activation on phenotype change of ICCs and colon electrical activity in hirschsprung's disease [D].Wuhan:Huazhong University of Science and Technology,2017.
[23] IKARASHI N, KON R, SUGIYAMA K.Aquaporins in the colon as a new therapeutic target in diarrhea and constipation [J].International Journal of Molecular Sciences, 2016, 17(7):1 172.
[24] CAO Y X, HE Y, WEI C, et al.Aquaporins alteration profiles revealed different actions of senna, sennosides, and sennoside a in diarrhea-rats [J].International Journal of Molecular Sciences, 2018, 19(10):3 210.
[25] BARICHELLO T, GENEROSO J S, SIMÕES L R, et al.Sodium butyrate prevents memory impairment by re-establishing BDNF and GDNF expression in experimental pneumococcal meningitis [J].Molecular Neurobiology, 2015, 52(1):734-740.
[26] SUPLY E, DE VRIES P, SORET R, et al.Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon [J].American Journal of Physiology-Gastrointestinal and Liver Physiology, 2012, 302(12):1 373-1 380.