疏肝健脾法对腹泻型肠易激综合征大鼠焦虑抑郁样行为及BDNF表达的影响
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摘要
目的:检测疏肝健脾法肠激安方对腹泻型肠易激综合征(IBS-D)大鼠焦虑抑郁样行为及脑源性神经营养因子(BDNF)的影响,探讨其改善IBS-D的作用机制。方法:采用"三因素"法(母婴分离+醋酸刺激+束缚应激)制备肝郁脾虚型IBS-D大鼠模型,造模成功后随机分为模型组、匹维溴铵组、肠激安方高、低剂量组,另设正常组,各6只,连续给药14 d,正常和模型组给予等体积生理盐水。观察IBS-D大鼠的焦虑抑郁样行为和海马神经元形态,检测海马、结肠中BDNF的基因、蛋白表达。结果:与正常组比较,模型组糖水偏好值、旷场实验相关指标水平减少(P<0.05),海马、结肠组织中BDNF mRNA及蛋白表达升高(P<0.05)。与模型组比较,肠激安方高、低剂量组的糖水偏好值、旷场实验相关指标水平升高(P<0.05),海马、结肠组织中BDNF mRNA及蛋白的表达下降(P<0.05)。结论:疏肝健脾法可明显改善IBS-D焦虑抑郁样行为,下调结肠、海马中BDNF表达水平,这可能是其改善IBS-D的作用机制之一。
Objective:To examine the effects and mechanism of smoothing liver and strengthening spleen method(Changji'an Formula) on anxiety-and depression-like behaviors and brain-derived neurotrophic factor(BDNF) in diarrehae-irritable bowel syndrome(IBS-D) model of rats.Methods:IBS-D rat model was established by using separation of breast milk,stimulation of acetic acid and constraint of four limbs.All model rats were randomly divided into the model control group,the Pinaverium Bromide group,the high and low dose of Changji′an Formula groups,six in each group.All medication lasted for 14 successive days.Another 6 normal rats were in the blank control group.Equal volume of saline was given to normal and model rats.After medication,we observed the IBS-D rat anxiety-and depression-like behaviors,the morphological character of hippocampus neurons,and detected the gene and protein expression of BDNF in hippocampus and colon.Results:Compared to the normal group,sugar water percentage preference and open field test related indictors level were significantly reduced(P<0.05) in rats of model group.The mRNA and protein expression of BDNF in hippocampus and colon of IBS-D rats were significantly increased(P<0.05).Compared to the model group,the sugar water percentage preference and open field test related indictors level wre obviously increased in the high and low dose of Changji′an Formula groups(P<0.05),and the mRNA and protein expression of BDNF was significantly lower in the high and low dose of Changji′an Formula groups(P<0.05).Conclusion:Smoothing liver and strengthening spleen method has obvious effect on IBS-D of anxiety-and depression-like behaviors,and reduces the expression level of BDNF in the hippocampus and the colon,which may contribute to the improvement of mechanism on IBS-D.
Objective:To examine the effects and mechanism of smoothing liver and strengthening spleen method(Changji'an Formula) on anxiety-and depression-like behaviors and brain-derived neurotrophic factor(BDNF) in diarrehae-irritable bowel syndrome(IBS-D) model of rats.Methods:IBS-D rat model was established by using separation of breast milk,stimulation of acetic acid and constraint of four limbs.All model rats were randomly divided into the model control group,the Pinaverium Bromide group,the high and low dose of Changji′an Formula groups,six in each group.All medication lasted for 14 successive days.Another 6 normal rats were in the blank control group.Equal volume of saline was given to normal and model rats.After medication,we observed the IBS-D rat anxiety-and depression-like behaviors,the morphological character of hippocampus neurons,and detected the gene and protein expression of BDNF in hippocampus and colon.Results:Compared to the normal group,sugar water percentage preference and open field test related indictors level were significantly reduced(P<0.05) in rats of model group.The mRNA and protein expression of BDNF in hippocampus and colon of IBS-D rats were significantly increased(P<0.05).Compared to the model group,the sugar water percentage preference and open field test related indictors level wre obviously increased in the high and low dose of Changji′an Formula groups(P<0.05),and the mRNA and protein expression of BDNF was significantly lower in the high and low dose of Changji′an Formula groups(P<0.05).Conclusion:Smoothing liver and strengthening spleen method has obvious effect on IBS-D of anxiety-and depression-like behaviors,and reduces the expression level of BDNF in the hippocampus and the colon,which may contribute to the improvement of mechanism on IBS-D.
引文
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[15] 董宁,赵瑞珍,徐硕,等.丹栀逍遥散对广泛性焦虑大鼠海马齿状回神经干细胞增殖与分化能力的干预作用[J].北京中医药,2015,34(1):63-66.
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[17] 李则挚,洪武,方贻儒.脑源性神经营养因子在抑郁症发作病理机制中的作用[J].上海交通大学学报:医学版,2010,30(6):651-655.
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[19] 于岩波.肠易激综合征神经调控异常分子机制的研究[D].济南:山东大学,2011.
[20] 唐洪梅,李得堂,黄樱华,等.肠激安方抑制肠易激综合征模型大鼠肥大细胞的实验研究[J].中药新药与临床药理,2008,19(6):464-466.
[21] Duman R S,Monteggia L M. A neurotrophic model for stress-related mood disorders[J]. Biol Psychiatry,2006,59(12):1116-1127.
[22]王国华.抗抑郁药物的神经可塑性促进作用及机制研究[D].广州:南方医科大学,2013.
[23] Larsen M H,Mikkelsen J D,Hay-Schmidt A,et al. Regulation of brain-derived neurotrophic factor(BDNF)in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment[J]. J Psychiatr Res,2010,44(13):808-816.
[24]詹丽杏,李兆申,邹多武,等.匹维溴铵治疗肠易激综合征的临床疗效及改变肛门直肠动力和内脏敏感性研究[J].中华消化杂志,2002,22(8):25-28.
[25]凌萌智.匹维溴铵治疗腹泻型肠易激综合征疗效观察[J].现代中西医结合杂志,2015,24(2):167-169.
[2] 沈淑华,黄宣,吕宾,等.腹泻型肠易激综合征证型及证候要素的文献研究[J].中华中医药杂志,2013,28(5):1538-1540.
[3] 黄绍刚,丁冠福,黎颖婷.基于聚类分析的腹泻型肠易激综合征中医证候特征研究[J].新中医,2013,45(8):40-43.
[4] 张科,曹蕊芸,诸孟娟,等.腹泻型肠易激综合征中医证型与焦虑、抑郁状态的相关性研究[J].辽宁中医杂志,2016,43(1):89-91.
[5] 丘振文.肠激安胶囊的主要药效学及干预腹泻型IBS的作用机理研究[D].广州:广州中医药大学,2008.
[6] 唐洪梅.肠激安胶囊制剂学及干预腹泻型肠易激综合征机理研究[D].广州:广州中医药大学,2007.
[7] 林玉,张瑞桐,兰明,等.BDNF-TrkB信号通路与焦虑障碍的产生[J].生命的化学,2013,33(6):668-672.
[8] 田相娟,王美萍.BDNF基因与抑郁[J].心理科学进展,2016,24(10):1583-1591.
[9] 焦黛妍,孙建华.脑源性神经营养因子在肠道高敏感中的研究进展[J].胃肠病学,2014,19(2):121-123.
[10] 刘迪,唐倩倩,曹君利.脑源性生长因子参与疼痛-抑郁共病的研究进展[J].中国药理学通报,2015,31(1):26-30.
[11] Joo Y E.Increased Expression of Brain-derived Neurotrophic Factor in Irritable Bowel Syndrome and Its Correlation With Abdominal Pain[J].J Neurogastroenterol Motil,2013,19(1):109-111.
[12] 涂星.疏肝健脾止泻复方中药对IBS-D模型大鼠神经—内分泌—免疫网络的调控机制研究[D].广州:广州中医药大学,2015.
[13] 柴玉娜,黄育生,唐洪梅,等.疏肝健脾法肠激安方对IBS-D大鼠免疫功能的影响[J].中国实验方剂学杂志,2016,22(21):93-98.
[14] 傅锦华,刘勇,王清勇,等.舒肝解郁胶囊对抑郁模型大鼠海马神经元凋亡及脑组织caspase-3蛋白表达的影响[J].中南大学学报:医学版,2012,37(12):1198-1204.
[15] 董宁,赵瑞珍,徐硕,等.丹栀逍遥散对广泛性焦虑大鼠海马齿状回神经干细胞增殖与分化能力的干预作用[J].北京中医药,2015,34(1):63-66.
[16] 林玉,张瑞桐,兰明,等.BDNF-TrkB信号通路与焦虑障碍的产生[J].生命的化学,2013,33(6):668-672.
[17] 李则挚,洪武,方贻儒.脑源性神经营养因子在抑郁症发作病理机制中的作用[J].上海交通大学学报:医学版,2010,30(6):651-655.
[18] Ulmann L,Hatcher J P,Hughes J P,et al.Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain[J].J Neurosci,2008,28(44):11263-11268.
[19] 于岩波.肠易激综合征神经调控异常分子机制的研究[D].济南:山东大学,2011.
[20] 唐洪梅,李得堂,黄樱华,等.肠激安方抑制肠易激综合征模型大鼠肥大细胞的实验研究[J].中药新药与临床药理,2008,19(6):464-466.
[21] Duman R S,Monteggia L M. A neurotrophic model for stress-related mood disorders[J]. Biol Psychiatry,2006,59(12):1116-1127.
[22]王国华.抗抑郁药物的神经可塑性促进作用及机制研究[D].广州:南方医科大学,2013.
[23] Larsen M H,Mikkelsen J D,Hay-Schmidt A,et al. Regulation of brain-derived neurotrophic factor(BDNF)in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment[J]. J Psychiatr Res,2010,44(13):808-816.
[24]詹丽杏,李兆申,邹多武,等.匹维溴铵治疗肠易激综合征的临床疗效及改变肛门直肠动力和内脏敏感性研究[J].中华消化杂志,2002,22(8):25-28.
[25]凌萌智.匹维溴铵治疗腹泻型肠易激综合征疗效观察[J].现代中西医结合杂志,2015,24(2):167-169.