白藜芦醇对肠易激综合征大鼠脑源性神经营养因子系统表达的影响

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1675 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要

目的：探讨白藜芦醇对肠易激综合征（IBS）模型大鼠抑郁焦虑样行为和肠道动力紊乱、内脏高敏性的改善作用及其作用机制。方法：将42只SD大鼠随机分为正常对照组、慢急性联合应激模型组、不同剂量白藜芦醇组（10、20和40 mg/kg）、氟西汀组以及地西泮组。采用慢急性联合应激建立IBS模型，通过强迫游泳、大理石掩埋实验分别评估动物抑郁、焦虑样行为，以肠道动力学测试和内脏敏感性实验来测定大鼠肠道动力和肠道敏感程度。采用Western blot法测定大鼠海马、额叶、回肠和结肠脑源性神经营养因子（BDNF）水平。结果：慢急性联合应激模型组与正常对照组大鼠相比，强迫游泳不动时间显著增加（P＜0.01），大理石掩埋（P＜0.01）和排便颗数明显增多（P＜0.01），腹壁撤退反射评分升高（20 mmHg：P＜0.05；40 mmHg：P＜0.05；60 mmHg：P＜0.01；80 mmHg：P＜0.01）；海马和额叶中BDNF表达水平下降（P＜0.01），结肠和回肠BDNF表达增加（P＜0.05）。在连续22 d给予白藜芦醇治疗后，上述现象都得到不同程度改善。结论：白藜芦醇能够改善IBS大鼠焦虑抑郁、肠道动力紊乱和内脏敏感性增加的现象，且这一作用很可能与其调节脑内与肠道中BDNF系统表达相关。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	张健波
	朱娜萍
	陈洁
	刘开平
	叶涵
	许文
	潘建春

关键词 ：白藜芦醇, 肠易激综合征, 脑源性神经营养因子, 慢急性联合应激, 大鼠

Abstract：Objective: To investigate the effect of resveratrol on depression- and anxiety-like behaviors, intestinal motility and visceral sensitivity in rats with irritable bowel syndrome. Methods: Forty-two SD rats were randomly divided into normal control group, chronic-acute combined stress (CACS) group, resveratrol group with different doses (10, 20 and 40 mg/kg), fluoxetine group and diazepam group. Twenty-two day CACS was used to established CACS model. The depression- and anxiety-like behaviors were evaluated by forced swimming test and marble-burying task. Intestinal motility and visceral sensitivity were measured by intestinal motility test and AWR test. The levels of brain-derived neurotrophic factor (BDNF) in hippocampus, frontal cortex, ileum and colon were measured by Western blot. Results: Compared with the normal group, the duration of immobility time of forced swimming and the number of marble buried was significantly increased (P<0.01 and P<0.01, respectively); the number of fecal output (P<0.01) in the intestinal motility test and the abdominal withdrawal reflex (AWR) score were also increased in CACS group (20 mmHg: P<0.05; 40 mmHg: P<0.05; 60 mmHg: P<0.01; 80 mmHg: P<0.01). The expression of BDNF in hippocampus (P<0.01) and the frontal cortex (P<0.01) were decreased, while the expression of BDNF in colon (P<0.01) and ileum (P<0.05) were increased in the CACS group, as compared with the normal control group. After 22-day treatment with resveratrol, the above data have been improved. Conclusion: Resveratrol ameliorated the behavior of IBS rats, which is likely to be related to the regulation of BDNF expression in the brain and gut.

Key words： resveratrol irritable bowel syndrome brain-derived neurotrophic factor chronic acute combined stress rats

收稿日期: 2017-10-17

通讯作者: 潘建春，教授，硕士生导师，Email：wenzhoupan2003@163.com。

作者简介: 张健波（1992-），女，浙江宁波人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I3/178

[1] DROSSMAN D A, MORRIS C B, SCHNECK S, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit[J]. J Clin Gastroenterol, 2009, 43 (6): 541-550.
[2] KIBUNE N C, GARCIA M C, SILVA L S L, et al. Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities[J]. Rev Esp Enferm Dig, 2016, 108(2): 59-64.
[3] BENGTSON M B, AAMODT G, VATN M H, et al. Co-occurrence of IBS and symptoms of anxiety or depression, among Norwegian twins, is influenced by both heredity and intrauterine growth[J]. BMC Gastroenterol, 2015, 15: 9.
[4] JERNDAL P, RINGSTRöM G, AGERFORZ P, et al. Gastrointestinal-specific anxiety: an important factor for severity of GI symptoms and quality of life in IBS[J]. Neurogastroenterol Motil, 2010, 22(6): 646-e179.
[5] 王林, 潘建春. 白藜芦醇通过调节Ca2+浓度对小鼠外周疼痛的影响及作用机制[J]. 温州医科大学学报, 2018, 48(1): 53-56, 62.
[6] XU Y, WANG Z, YOU W, et al. Antidepressant-like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system[J]. Eur Neuropsychopharmacol, 2010, 20(6): 405-413.
[7] GE J F, XU Y Y, QIN G, et al. Resveratrol ameliorates the anxiety- and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt/β-Catenin pathway[J]. Front Endocrinol (Lausanne), 2016, 7: 44.
[8] ZOU N, LV H, LI J, et al. Changes in brain G proteins and colonic sympathetic neural signaling in chronic-acute combined stress rat model of irritable bowel syndrome (IBS)[J]. Transl Res, 2008, 152(6): 283-289.
[9] YU Y, WU S, LI J, et al. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling[J]. Metab Brain Dis, 2015, 30(1): 47-55.
[10] ZHAO Z, ZHANG L, GUO X D, et al. Rosiglitazone exerts an anti-depressive effect in unpredictable chronic mild-stress-induced depressive mice by maintaining Essential neuron autophagy and inhibiting excessive astrocytic apop-tosis[J]. Front Mol Neurosci, 2017, 10: 293.
[11] PORSOLT R D, LE P M, JALFRE M. Depression: a new animal model sensitive to antidepressant treatments[J]. Nature, 1977, 266(5604): 730-732.
[12] 许笑笑, 吴飞燕, 费宁, 等. 抑郁焦虑情绪与肠道炎症潜在交互作用探讨[J]. 温州医科大学学报, 2016, 46(5): 348-353, 358.
[13] BARONE F C, DEEGAN J F, PRICE W J, et al. Cold-restraint stress increases rat fecal pellet output and colonic transit[J]. Am J Physiol, 1990, 258(3 Pt 1): G329-337.
[14] AL-CHAER E D, KAWASAKI M, PASRICHA P J. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development[J]. Gastroenterology, 2000, 119(5): 1276-1285.
[15] FORD A C, LACY B E, TALLEY N J. Irritable Bowel Syn-drome[J]. N Engl J Med, 2017, 376(26): 2566-2578.
[16] GWEE K A, GHOSHAL U C, CHEN M. Irritable bowel syndrome in Asia: Pathogenesis, natural history, epidemiology, and management[J]. J Gastroenterol Hepatol, 2018, 33 (1): 99-110.
[17] CAMILLERI M, MCKINZIE S, BUSCIGLIO I, et al. Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome[J]. Clin Gastroenterol Hepatol, 2008, 6(7): 772-781.
[18] ELSENBRUCH S, ROSENBERGER C, ENCK P, et al. Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study[J]. Gut, 2010, 59(4): 489-495.
[19] LIU Y, ZHANG L, WANG X, et al. Similar fecal microbiota signatures in patients with diarrhea-predominant irritable bowel syndrome and patients with depression[J]. Clin Gastroenterol Hepatol, 2016, 14(11): 1602-1611.e5.
[20] TABRIZIAN K, SHAHRAKI J, BAZZI M, et al. Neuro-protective effects of resveratrol on carbon monoxide-induced toxicity in male rats[J]. Phytother Res, 2017, 31(9): 1310-1315.
[21] 李宁宁, 方秀才. 脑-肠轴在肠易激综合征发病中的作用[J]. 胃肠病学和肝病学杂志, 2013, 22(2): 163-166.
[22] TöRNBLOM H, DROSSMAN D A. Centrally targeted pharmacotherapy for chronic abdominal pain[J]. Neurogastroenterol Motil, 2015, 27(4): 455-467.
[23] WANG G, CHEN L, PAN X, et al. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling[J]. Oncotarget, 2016, 7(14): 17380-17392.
[24] MAQSOOD R, STONE T W. The Gut-Brain Axis, BDNF, NMDA and CNS disorders[J]. Neurochem Res, 2016, 41 (11): 2819-2835.
[25] 梁超, 徐斌. 脑源性神经营养因子在肠道中作用的研究进展[J]. 世界华人消化杂志, 2015, 23(35): 5649-5654.
[26] 周小江, 胡园, 刘屏. 脑源性神经营养因子与抑郁症的研究进展[J]. 生物化学与生物物理进展, 2011, 38(12): 1085-1090.
[27] GAWALI N B, BULANI V D, GURSAHANI M S, et al. Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway[J]. Brain Res, 2017, 1663: 66-77.
[28] MENDEZ-DAVID I, GUILLOUX J P, PAPP M, et al. S 47445 produces antidepressant- and anxiolytic-like effects through neurogenesis dependent and independent mecha-nisms[J]. Front Pharmacol, 2017, 8: 462.
[29] 赵宏宇, 陈飞雪, 曹静, 等. 脑组织海马区脑源性神经营养因子在焦虑调节内脏高敏感中的作用[J]. 山东大学学报(医学版), 2014, 52(3): 33-36.
[30] QUAN X, LUO H, FAN H, et al. Brain-derived neurotrophic factor contributes to colonic hypermotility in a chronic stress rat model[J]. Dig Dis Sci, 2015, 60(8): 2316-2326.
[31] DELAFOY L, GELOT A, ARDID D, et al. Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat[J]. Gut, 2006, 55(7): 940-945.
[32] 赵迎盼, 苏敏, 王凤云, 等. 肠安I号方对肠易激综合征内脏高敏感大鼠5-HT信号系统及海马BDNF mRNA表达的影响[J]. 中国中西医结合杂志, 2015, 35(10): 1228-1235.
[33] PARK S J, AHMAD F, PHILP A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases[J]. Cell, 2012, 148(3): 421-433.