针刺对应激性胃溃疡模型大鼠血清和下丘脑中GAS、SS和MT表达的影响
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摘要
目的从脑-肠轴角度分析胃肠疾病对睡眠的影响,为"胃不和则卧不安"理论提供现代科学支持。方法 SD大鼠随机分为正常组、模型组,针刺治疗组,药物治疗组,每组7只。采用束缚-浸水(restraint water-immersion stress,RWIS)应激法造大鼠胃溃疡模型;针刺治疗组选用"中脘""足三里",每天针刺20分钟,每5分钟行针30秒,药物组选用奥美拉唑肠溶片(0.2 mg/kg),每日一次灌胃给药,干预5天后取材,40 mg/kg戊巴比妥钠诱导大鼠睡眠,记录各组大鼠睡眠持续时间,Guth法计算胃黏膜损伤指数,和下酶联免疫法测定血清丘脑中胃泌素(gastrin,GAS)、生长抑素(somatostatin,SS)和褪黑素(melatonin,MT)的含量。结果模型组大鼠睡眠时间明显少于正常组(P<0.05),针刺治疗后睡眠时间明显延长(P<0.05);模型组大鼠胃黏膜损伤指数显著高于正常组(P<0.01),造胃溃疡模型成功;针刺组和药物组大鼠损伤指数较模型组明显降低(P<0.05)。模型组大鼠血清和下丘脑GAS较正常组含量均显著升高(P<0.01),MT、SS含量显著降低(P<0.01);针刺组和药物组大鼠血清和下丘脑GAS含量较模型组均明显降低(P<0.01),针刺组大鼠血清和下丘脑MT、SS的表达明显升高(P<0.01)。结论胃肠疾病与失眠密切相关,针刺"中脘""足三里"能够促进大鼠胃溃疡的愈合,改善大鼠睡眠,这与其降低外周和中枢GAS含量,增加SS、MT含量有关。
Objective To analysis the effects of gastrointestinal diseases on sleep from the angle of the "brain-gut axis ",to provide modern scientific support for the theory of"Inharmonious stomach leads to insomnia". Methods SD rats were randomly divided into the normal group,the model group,the acupuncture treatment group and the drug treatment group,7 rats in each group. The gastric ulcer model was induced by restraint and water-immersion stress( RWIS). The acupuncture treatment group were acupuncture at "Zhongwan","Zusanli",20 minutes a day,acupuncture of 30 seconds every 5 minutes.The rats in drug treatment group were treated with omeprazole enteric-coated tablets( 0.2 mg/kg),gavage ofmedicine once a day. After 5 days of intervention,40 mg/kg sodium pentobarbital was used to induce sleep,sleep duration of rats were recorded. The gastric mucosal injury index was calculated by Guth,and the contents of gastrin( GAS),somatostatin( somatostatin,SS) and melatonin( melatonin,MT) in thalamus were detected by enzyme linked immunosorbent assays. Results The sleep time of the rats in the model group was significantly less than that in the normal group( P< 0.05),and the sleep time was obviously prolonged after the acupuncture treatment( P< 0. 05). The gastric mucosal injury index in the model group was significantly higher than that of the normal group( P <0.01).The rats in the model group of serum and hypothalamic GAS were significantly increased compared with normal group( P < 0. 01),MT,SS content decreased significantly( P< 0. 01); the content of GAS in serum and hypothalamus of acupuncture treatment group and drug treatment group was significantly lower than that of model group( P<0.01). The expression of MT and SS in serum and hypothalamus of acupuncture treatment group increased significantly( P < 0. 01). Conclusion Gastrointestinal diseases and insomnia are closely related,acupuncture at"Zhongwan"and "Zusanli" can promote gastric ulcer healing,improve sleep in rats,which might contribute to decreasing the content of GAS and increasing the content of SS,MT in peripheral and central content.
Objective To analysis the effects of gastrointestinal diseases on sleep from the angle of the "brain-gut axis ",to provide modern scientific support for the theory of"Inharmonious stomach leads to insomnia". Methods SD rats were randomly divided into the normal group,the model group,the acupuncture treatment group and the drug treatment group,7 rats in each group. The gastric ulcer model was induced by restraint and water-immersion stress( RWIS). The acupuncture treatment group were acupuncture at "Zhongwan","Zusanli",20 minutes a day,acupuncture of 30 seconds every 5 minutes.The rats in drug treatment group were treated with omeprazole enteric-coated tablets( 0.2 mg/kg),gavage ofmedicine once a day. After 5 days of intervention,40 mg/kg sodium pentobarbital was used to induce sleep,sleep duration of rats were recorded. The gastric mucosal injury index was calculated by Guth,and the contents of gastrin( GAS),somatostatin( somatostatin,SS) and melatonin( melatonin,MT) in thalamus were detected by enzyme linked immunosorbent assays. Results The sleep time of the rats in the model group was significantly less than that in the normal group( P< 0.05),and the sleep time was obviously prolonged after the acupuncture treatment( P< 0. 05). The gastric mucosal injury index in the model group was significantly higher than that of the normal group( P <0.01).The rats in the model group of serum and hypothalamic GAS were significantly increased compared with normal group( P < 0. 01),MT,SS content decreased significantly( P< 0. 01); the content of GAS in serum and hypothalamus of acupuncture treatment group and drug treatment group was significantly lower than that of model group( P<0.01). The expression of MT and SS in serum and hypothalamus of acupuncture treatment group increased significantly( P < 0. 01). Conclusion Gastrointestinal diseases and insomnia are closely related,acupuncture at"Zhongwan"and "Zusanli" can promote gastric ulcer healing,improve sleep in rats,which might contribute to decreasing the content of GAS and increasing the content of SS,MT in peripheral and central content.
引文
[1]杨君.应激性溃疡的发病机制研究进展[J].中国急救医学,2007,27(11):1035-1038.
[2]张压西,石松.中医“胃不和则卧不安”理论与消化系疾病及失眠的关系[J].世界华人消化杂志,2012,20(5):380-384.
[3]黄迎华,李倩,杨萍,等.针刺对胃黏膜损伤大鼠睡眠时间及血清和海马中肿瘤坏死因子-α及白介素-25含量的影响[J].针刺研究,2015,40(2):131-135.
[4]刘雅楠,林成荫,吴焕淦,等.从脾胃论治针刺治疗失眠症临床观察[J].中国针灸,2015,35(8):768-772.
[5]闫亚南.预针刺对应激性胃溃疡模型大鼠睡眠时间及CRH含量的影响[J].针灸临床杂志,2016,32(3):67-70.
[6]Guth P H,Aures D,Paulsen G.To Pical as Pirin Plus HCl gastric lesions in the rat.Cyto Protective effect of Prostaglandin,cimetidine,and Probanthine.[J].Gastroenterology,1979,76(1):88-93.
[7]石剑峰.应激性溃疡防治的研究进展[J].现代预防医学,2013,40(1):166-167.
[8]杜海燕,王迎寒,张晓峰.脑-肠轴及其在肠易激综合征发病机制中的作用[J].承德医学院学报,2014,31(2):151-153.
[9]Sever K,Ozbek C,Goktas B,et al.Astrointestinal com Pli-cations after o Pen heart surgery:incidence and determinants of risk factors[J].Angiology,2014,65(5):425-429.
[10]张丽霞,黄慧,李贵霞,等.血清瘦素、肿瘤坏死因子与儿童厌食症的相关性研究[J].临床荟萃,2009,24(21):1903-1904.
[11]王红卫.肿瘤坏死因子-α基因多态性与幽门螺杆菌感染的胃溃疡及吸烟的相关性分析[J].实用医技杂志,2012,19(3):229-231.
[12]彭静微,韩旭.褪黑素与睡眠的关系探讨[J].国际中医中药杂志,2014,36(6):550-551.
[13]Konakchieva R,Mitev Y,Almeida O F,et al.Chronic melatonin treatment and the hy Pothalamo-Pituitary-adrenal axis in the rat:Attenuation of the secretory res Ponse to stress and effects on hyPothalamic neuro Pe Ptide content and release[J].Biology of the Cell,1997,89(9):587-596.
[14]Roehrs T,Roth T.Insomnia Pharmacotherapy[J].Journal of the American Society for Experimental Neuro Therapeutics,2012,9(4):728-738.
[15]Dubocovich ML,Delagrange P,Krause DN et al.International Union of Basic and Clinical Pharmacology.LXXV.Nomenclature,classification,and Pharmacology of G Protein-cou Pled melatonin receptors.[J].Pharmacological reviews,2010,62(3):343-380.
[16]Zhong LY,Yang ZH,Li XP,et al.Protective effects of melatonin against the damages of neuroendocrine-immune induced by li Po Polysaccharide in diabetic rats[J].Ex P Clin Endocrinol Diabetes,2009,117(9):463-469.
[17]孙光斌,赵巍,王德宝.褪黑素在胃肠功能调节中的作用[J].中国综合临床,2001,17(12):890-891.
[18]Lewinski A,Rybicka I,Wajs E,et al.Influence of Pineal indolamines on the mitotic activity of gastric and colonic micosa e Pithelial cells in the ract interaction with ome Prazole.J Pineal Res,1991,10(2):104-108.
[19]Guo H,Zhang R R,Zhu S F,et al.Progress of Research on AcuPuncture for Regulating Gastrointestinal Motility in Acute Pancreatitis[J].Journal of Clinical Acu Puncture&Moxibustion,2013,33(5):35.
[20]Reicher JJ,Mindelzun R.Case re Port:benign gastric ulcer erosion leading to a gastro Pericardial fistula in a Patient with no known risk factors[J].Clinical Imaging,2014,38(4):547-549.
[21]周德生,朱婷,胡华,等.生长抑素、胃泌素与应激性溃疡的中医药干预研究进展[J].中西医结合心脑血管病杂志,2010,8(5):597-600.
[22]王颂歌,余会丽,马明,等.抗菌药物对幽门螺杆菌感染胃溃疡患者血清炎症因子及胃泌素指标的影响[J].中华医院感染学杂志,2016,26(11):2470-2472.
[23]陶彦谷,黄启辉.香砂六君子汤联合胃复春治疗胃溃疡的疗效及对血清胃泌素及胃动素水平的影响[J].现代消化及介入诊疗,2015,(4):360-362.
[24]章春花.用生长抑素对胃溃疡所致上消化道出血患者进行辅助治疗的效果分析[J].当代医药论丛,2016,4(19):63-64.
[25]Coin I,Katritch V,Sun T,et al.Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR.[J].Cell,2013,155(6):1258-1269.
[26]曾永明,陈广灿,李威,等.生长抑素在肠梗阻治疗中的作用[J].实用全科医学,2006,4(3):258-259.
[27]欧阳艳君,张艳梅,李炳东,等.雷贝拉唑三联疗法对活动期胃溃疡患者组织学愈合质量及溃疡复发的作用分析[J].现代中西医结合杂志,2014,23(20):2196-2198.
[28]高洋,杨波,严兴科.针灸治疗胃溃疡的机理研究进展[J].上海针灸杂志,2008,27(9):48-50.
[29]赵保民,黄裕新,张伟,等.电针对大鼠胃黏膜胃泌素和EGFR表达及Ag NOR的影响[J].第四军医大学学报,2001,22(9):782-785.
[30]黄龙,于庆生,潘晋方,等.针刺对腹部术后胃肠功能恢复及胃肠激素分泌的影响[J].安徽中医药大学学报,2015,34(5):52-55.
[31]杨萍,彭磊,李捷婷,等.针刺对胃黏膜损伤大鼠睡眠时间的改变及血清和纹状体多巴胺含量的影响[J].针刺研究,2014,39(1):52-57.
[32]韩焱晶,代伟伟,彭磊,等.针刺对应激性胃黏膜损伤大鼠血浆和下丘脑中β-内啡肽含量的影响[J].针刺研究,2011,36(5):341-346.
[2]张压西,石松.中医“胃不和则卧不安”理论与消化系疾病及失眠的关系[J].世界华人消化杂志,2012,20(5):380-384.
[3]黄迎华,李倩,杨萍,等.针刺对胃黏膜损伤大鼠睡眠时间及血清和海马中肿瘤坏死因子-α及白介素-25含量的影响[J].针刺研究,2015,40(2):131-135.
[4]刘雅楠,林成荫,吴焕淦,等.从脾胃论治针刺治疗失眠症临床观察[J].中国针灸,2015,35(8):768-772.
[5]闫亚南.预针刺对应激性胃溃疡模型大鼠睡眠时间及CRH含量的影响[J].针灸临床杂志,2016,32(3):67-70.
[6]Guth P H,Aures D,Paulsen G.To Pical as Pirin Plus HCl gastric lesions in the rat.Cyto Protective effect of Prostaglandin,cimetidine,and Probanthine.[J].Gastroenterology,1979,76(1):88-93.
[7]石剑峰.应激性溃疡防治的研究进展[J].现代预防医学,2013,40(1):166-167.
[8]杜海燕,王迎寒,张晓峰.脑-肠轴及其在肠易激综合征发病机制中的作用[J].承德医学院学报,2014,31(2):151-153.
[9]Sever K,Ozbek C,Goktas B,et al.Astrointestinal com Pli-cations after o Pen heart surgery:incidence and determinants of risk factors[J].Angiology,2014,65(5):425-429.
[10]张丽霞,黄慧,李贵霞,等.血清瘦素、肿瘤坏死因子与儿童厌食症的相关性研究[J].临床荟萃,2009,24(21):1903-1904.
[11]王红卫.肿瘤坏死因子-α基因多态性与幽门螺杆菌感染的胃溃疡及吸烟的相关性分析[J].实用医技杂志,2012,19(3):229-231.
[12]彭静微,韩旭.褪黑素与睡眠的关系探讨[J].国际中医中药杂志,2014,36(6):550-551.
[13]Konakchieva R,Mitev Y,Almeida O F,et al.Chronic melatonin treatment and the hy Pothalamo-Pituitary-adrenal axis in the rat:Attenuation of the secretory res Ponse to stress and effects on hyPothalamic neuro Pe Ptide content and release[J].Biology of the Cell,1997,89(9):587-596.
[14]Roehrs T,Roth T.Insomnia Pharmacotherapy[J].Journal of the American Society for Experimental Neuro Therapeutics,2012,9(4):728-738.
[15]Dubocovich ML,Delagrange P,Krause DN et al.International Union of Basic and Clinical Pharmacology.LXXV.Nomenclature,classification,and Pharmacology of G Protein-cou Pled melatonin receptors.[J].Pharmacological reviews,2010,62(3):343-380.
[16]Zhong LY,Yang ZH,Li XP,et al.Protective effects of melatonin against the damages of neuroendocrine-immune induced by li Po Polysaccharide in diabetic rats[J].Ex P Clin Endocrinol Diabetes,2009,117(9):463-469.
[17]孙光斌,赵巍,王德宝.褪黑素在胃肠功能调节中的作用[J].中国综合临床,2001,17(12):890-891.
[18]Lewinski A,Rybicka I,Wajs E,et al.Influence of Pineal indolamines on the mitotic activity of gastric and colonic micosa e Pithelial cells in the ract interaction with ome Prazole.J Pineal Res,1991,10(2):104-108.
[19]Guo H,Zhang R R,Zhu S F,et al.Progress of Research on AcuPuncture for Regulating Gastrointestinal Motility in Acute Pancreatitis[J].Journal of Clinical Acu Puncture&Moxibustion,2013,33(5):35.
[20]Reicher JJ,Mindelzun R.Case re Port:benign gastric ulcer erosion leading to a gastro Pericardial fistula in a Patient with no known risk factors[J].Clinical Imaging,2014,38(4):547-549.
[21]周德生,朱婷,胡华,等.生长抑素、胃泌素与应激性溃疡的中医药干预研究进展[J].中西医结合心脑血管病杂志,2010,8(5):597-600.
[22]王颂歌,余会丽,马明,等.抗菌药物对幽门螺杆菌感染胃溃疡患者血清炎症因子及胃泌素指标的影响[J].中华医院感染学杂志,2016,26(11):2470-2472.
[23]陶彦谷,黄启辉.香砂六君子汤联合胃复春治疗胃溃疡的疗效及对血清胃泌素及胃动素水平的影响[J].现代消化及介入诊疗,2015,(4):360-362.
[24]章春花.用生长抑素对胃溃疡所致上消化道出血患者进行辅助治疗的效果分析[J].当代医药论丛,2016,4(19):63-64.
[25]Coin I,Katritch V,Sun T,et al.Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR.[J].Cell,2013,155(6):1258-1269.
[26]曾永明,陈广灿,李威,等.生长抑素在肠梗阻治疗中的作用[J].实用全科医学,2006,4(3):258-259.
[27]欧阳艳君,张艳梅,李炳东,等.雷贝拉唑三联疗法对活动期胃溃疡患者组织学愈合质量及溃疡复发的作用分析[J].现代中西医结合杂志,2014,23(20):2196-2198.
[28]高洋,杨波,严兴科.针灸治疗胃溃疡的机理研究进展[J].上海针灸杂志,2008,27(9):48-50.
[29]赵保民,黄裕新,张伟,等.电针对大鼠胃黏膜胃泌素和EGFR表达及Ag NOR的影响[J].第四军医大学学报,2001,22(9):782-785.
[30]黄龙,于庆生,潘晋方,等.针刺对腹部术后胃肠功能恢复及胃肠激素分泌的影响[J].安徽中医药大学学报,2015,34(5):52-55.
[31]杨萍,彭磊,李捷婷,等.针刺对胃黏膜损伤大鼠睡眠时间的改变及血清和纹状体多巴胺含量的影响[J].针刺研究,2014,39(1):52-57.
[32]韩焱晶,代伟伟,彭磊,等.针刺对应激性胃黏膜损伤大鼠血浆和下丘脑中β-内啡肽含量的影响[J].针刺研究,2011,36(5):341-346.