蜘蛛香环烯醚萜对肠易激综合征的治疗作用及机理探讨
|
摘要
肠易激综合征(irritable bowel syndrome,IBS)是一种胃肠功能紊乱性疾病,以腹痛或腹部不适,伴有大便性状改变和排便习惯改变为特征。根据临床症状,可分为腹泻型、便秘型和腹泻便秘交替型。流行病学调查显示,在健康人群中该病的患病率高达10%～20%,占到消化科就诊人数的50%以上。其病理生理学基础主要是胃肠动力学异常和内脏敏感性增高,但其具体机制尚不明确。中医将肠易激综合征归于“肠郁”的范畴,认为其病机多为肝郁脾虚,气血不和所致,治疗多用疏肝解郁,健脾化湿为主。
蜘蛛香是一种常用的苗药,可理气止痛、消炎止泻、祛风除湿。用于脘腹胀痛,消化不良,腹泻,痢疾,风湿痹痛,腰膝酸软等。通过前期研究证实了蜘蛛香应用于治疗IBS有显著疗效,蜘蛛香原粉对慢性应激所致IBS大鼠模型的胃肠功能及精神神经活动的异常均具有改善作用。经过筛选环烯醚萜对小鼠胃肠运动亢进和精神神经活动异常作用最强,故确定有效部位是环烯醚萜。
课题通过观察蜘蛛香环烯醚萜对正常及IBS模型动物的胃肠道功能、精神活动的影响,以及蜘蛛香环烯醚萜干预下IBS大鼠结肠、血清、中枢5-HT含量,结肠5-HTR3A受体的mRNA和色氨酸羟化酶(TPH1)的mRNA表达,结肠和血浆中SP和VIP含量以及结肠中肥大细胞分布,探讨蜘蛛香环烯醚萜对腹泻型IBS的治疗作用及其作用机理,为临床治疗IBS提供实验依据。
1蜘蛛香环烯醚萜对胃肠功能的作用
目的:探讨蜘蛛香环烯醚萜对胃肠功能的影响
1.1蜘蛛香环烯醚萜对正常小鼠胃肠功能的作用
方法:正常小鼠灌胃给予蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg与空白组和越鞠保和丸组对照,给药4日后测定动物的胃排空率和小肠推进率。
结果:蜘蛛香环烯醚萜35.6mg/kg、17.8mg/kg组能减缓胃排空和小肠推作用(P<0.05),说明蜘蛛香环烯醚萜对正常小鼠胃肠功能有一定的抑制作用。
1.2蜘蛛香环烯醚萜对利血平化小鼠胃肠功能的作用
方法:小鼠每日腹腔注射利血平造模,同时灌胃给予蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg与空白组、模型组和越鞠保和丸组对照,给药6日后测定动物的胃排空率和小肠推进率。
结果:腹腔注射利血平后,与正常组比较,模型组小肠推进率增高(P<0.05)。与模型组相比,蜘蛛香环烯醚萜71.2mg/kg组可减缓胃排空(P<0.05),小肠推进没有明显差异。蜘蛛香环烯醚萜35.6mg/kg组可减缓胃排空和小肠推进(P<0.05);蜘蛛香环烯醚萜17.8mg/kg组可减缓小肠推进(P<0.05),胃排空没有明显差异。说明蜘蛛香环烯醚萜可改善利血平导致的胃肠运动亢进。
1.3蜘蛛香环烯醚萜对慢性应激所致IBS大鼠胃肠功能的作用
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。进行慢性应激实验:对照组14-15只/笼,不给任何刺激,其余各组每笼一只孤养,并加以慢性不可预见性的刺激,造模28天,造模期间同时给药。检测各组动物腹部回撤反射压力阈值和2h内排便粒数。
结果:造模后,模型组动物疼痛压力阈值与最大耐受压力阈值均明显降低(P<0.01),表明动物内脏敏感性增高,同时动物排便量明显增多(P<0.01)。蜘蛛香环烯醚萜各给药组动物与模型组比较,疼痛压力阈值与最大耐受压力阈值均增加,其中蜘蛛香环烯醚萜24.92mg/kg组和12.46mg/kg组作用极显著(P<0.001)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组动物排便粒数显著减少,与模型组相比有显著差异(P<0.05)。表明蜘蛛香环烯醚萜可改善应激所致IBS大鼠模型的胃肠功能,降低内脏敏感性,减少排便数。
结论:IBS是一种胃肠紊乱性疾病,临床表现为腹痛、腹泻或者便秘等消化道症状,症状持续存在或间歇发作。蜘蛛香环烯醚萜可以减缓正常小鼠的胃肠运动和利血平化小鼠的胃肠功能亢进,降低慢性应激所致IBS模型大鼠的内脏敏感性,显著减少了IBS模型大鼠的排便数量,从而改善腹泻型IBS的临床症状。
2蜘蛛香环烯醚萜对神经系统功能的影响
目的:探讨蜘蛛香环烯醚萜对精神活动的影响
2.1蜘蛛香环烯醚萜对慢性应激所致IBS大鼠精神活动的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。检测各组动物敞箱试验得分和糖水偏嗜度。
结果:蜘蛛香环烯醚萜各给药组动物与模型组相比,敞箱试验水平运动得分与垂直运动得分增加,蔗糖偏嗜度提高。
2.2蜘蛛香环烯醚萜对醋酸所致小鼠疼痛的影响
方法:小鼠随机分为对照组、蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg组、阿司匹林组。给药6日后腹腔注射0.6%醋酸,观察扭体潜伏期,前10min扭体次数,后10min扭体次数,总共20min扭体次数。
结果:与对照组相比,蜘蛛香环烯醚萜各给药组扭体潜伏期无明显变化,前10min扭体次数,后10min扭体次数,总共20min扭体次数均明显减少(P<0.01)。表明蜘蛛香环烯醚萜对化学刺激所致疼痛,有显著的镇痛作用。
结论:蜘蛛香为缬草属植物,现代药理研究发现其有很好的镇静催眠和抗焦虑抗抑郁作用。本实验研究发现蜘蛛香环烯醚萜通过增强慢性应激所致的IBS模型大鼠的活动能力和兴趣缺失,降低摄食量,对精神活动有一定的改善作用。同时,蜘蛛香环烯醚萜可显著降低醋酸所致小鼠的扭体次数,说明其有良好的镇痛作用。
3蜘蛛香环烯醚萜治疗肠易激综合征机理
3.1蜘蛛香环烯醚萜对5-HT神经递质的影响
3.1.1蜘蛛香环烯醚萜对外周和中枢5-HT含量的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠结肠、血清和脑中5HT、5-HIAA的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取血清、结肠和下丘脑以高压液相法检测5-HT和5-HIAA含量,取脑以免疫组化法观察海马和杏仁核5-HT含量,并用imag-pro plus图像分析软件对5-HT免疫染色阳性细胞面积(Area)、积分光密度(IOD)进行半定量分析。
结果:对结肠5-HT的影响造模后,模型组动物结肠中5-HT含量明显增加,5-HIAA含量及5-HT/5-HIAA比值无明显变化。蜘蛛香环烯醚萜各组均可明显降低结肠中5-HT的含量(P<0.05),24.92mg/kg组和6.23mg/kg可显著降低5-HT/5-HIAA比值(P<0.05),24.92mg/kg可明显降低结肠中5-HIAA的含量(P<0.05)。
对血清5-HT的影响造模后,模型组动物血清中5-HT含量明显增加(P<0.01),5-HIAA含量无明显变化,5-HT/5-HIAA比值增加(P<0.05)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组可降低血清中5-HT的含量及5-HT/5-HIAA比值(P<0.05),但5-HIAA含量无明显变化。
对下丘脑5-HT的影响模型组动物下丘脑中5-HT含量明显下降(P<0.05),5-HIAA及5-HT/5-HIAA变化不明显。蜘蛛香12.46mg/kg、6.23mg/kg剂量组可明显升高5-HT(P<0.05),但5-HT/5-HIAA没有明显变化。
对海马和杏仁核5-HT的影响造模后,模型组大鼠阳性细胞面积和积分光密度降低(P<0.05)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组较模型组有明显上升(P<0.05)。
以上结果表明蜘蛛香环烯醚萜可以降低外周IBS模型大鼠结肠、血清的5-HT含量,可升高中枢下丘脑、海马及杏仁核中的5-HT含量。
3.1.2蜘蛛香环烯醚萜对大鼠5-HT合成限速酶的影响
目的:蜘蛛香环烯醚萜对慢性应激所致IBS大鼠色氨酸羟化酶mRNA表达的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取动物肛门上方3cm处结肠,以RT-PCR方法检测各组及蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组结肠的TPH1表达。
结果:造模后,模型组和各用药组之间TPH1 mRNA水平差异不显著。表明蜘蛛香环烯醚萜不影响色氨酸羟化酶的转录表达。
3.1.3蜘蛛香环烯醚萜对5-HT受体的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠5-HT3受体mRNA表达的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取动物肛门上方3cm处结肠,以RT-PCR方法检测各组及蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组结肠的mRNA表达。
结果:造模后,模型组的5-HTR3A/β-Actin比值明显高于对照组,说明慢性应激可引起大鼠结肠的5-HTR3A表达上调;蜘蛛香环烯醚萜组与模型组相比,5-HTR3A/β-Actin比值显著降低,5-HTR3A受体表达水平发生了相应下调。表明蜘蛛香环烯醚萜可抑制5-HT3A受体的转录。
结论:蜘蛛香环烯醚萜通过降低结肠、血清中5-HT含量,下调结肠5-HTR3A受体表达水平改善IBS胃肠道症状;其对5-HT含量的影响不是通过抑制色氨酸羟化酶实现的。造模后,中枢5-HT呈现降低趋势,这可能是导致动物出现活动能力下降和兴趣缺失的原因之一,蜘蛛香环烯醚萜可以增加下丘脑、海马和杏仁核中5-HT含量,推断蜘蛛香环烯醚萜可通过干预中枢的5-HT通路来改善IBS精神症状。
3.2蜘蛛香环烯醚萜对胃肠激素的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠SP和VIP的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。除对照组外,其余各组进行慢性应激实验。以放免法检测动物结肠和血浆中SP和VIP含量。
结果:对结肠SP和VIP的影响造模后,模型组结肠中SP有升高趋势,VIP有降低趋势,但均无统计学意义。蜘蛛香环烯醚萜各剂量组结肠中SP较模型组有降低趋势,VIP则有升高趋势,可降低SP/VIP值。
对血浆SP和VIP的影响造模后,模型组大鼠血浆中SP和VIP均上升,其中VIP上升明显(P<0.05)。蜘蛛香环烯醚萜各组对血浆中SP和VIP有下降趋势,其中24.92mg/kg组较模型组下降明显(P<0.05),6.23mg/kg组SP下降显著(P<0.05)。
结论:蜘蛛香环烯醚萜可能通过降低结肠和血浆中SP含量,降低结肠SP/VIP值,降低内脏敏感性,改善胃肠功能亢进所出现的症状。
3.3蜘蛛香环烯醚萜对免疫系统的影响
目的:蜘蛛香环烯醚萜对慢性应激所致IBS大鼠肥大细胞的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。除对照组外,其余各组进行慢性应激实验。取距肛门3cm处的结肠行甲苯胺蓝染色,以低倍显微镜观察肥大细胞分布。
结果:造模后,模型组较对照组肥大细胞明显增多,与模型组比较,蜘蛛香环烯醚萜各组结肠粘膜固有层及粘膜下层血管周围肥大细胞数量减少。表明蜘蛛香环烯醚萜可能减少结肠中肥大细胞数量。
结论:蜘蛛香环烯醚萜可能通过降低肥大细胞渗出,调节免疫系统状态参与IBS的治疗。
综上所述,蜘蛛香环烯醚萜可以抑制胃肠功能亢进,降低内脏敏感性,改善精神状态,并具有良好的镇痛作用,从而改善腹泻型IBS的临床症状。其机制可能涉及了蜘蛛香环烯醚萜对外周和中枢的5-HT系统、胃肠激素系统及肥大细胞免疫系统的调节作用。
课题首次确定了蜘蛛香治疗IBS的有效部位为环烯醚萜类成分,并对其作用机制从神经递质,胃肠激素及免疫系统等不同方面进行了研究,为发掘具有我国民族特色的药用资源,深入探讨其物质基础和作用机理提供了科学依据。
Irritable bowel syndrome is one of the disorders of gastrointestinal function,with the characteristic of abdominal pain or discomfort,associated with characters change and habit change in stool.Epidemiological survey shows that the rate of this disease is as high as 10%to 20%in healthy people,accounting for more than 50%of the number of patients coming to the digestion department.Its basis of pathophysiology is mainly based on the abnormal of gastrointestinal kinetics and the increased visceral sensitivity,but the specific mechanism is not clear.The Chinese medicine attributed the irritable bowel syndrome to the scope of "intestinal depression",that the pathogenesis are most the liver depression and spleen deficiency and uncoordination of qi and blood,the main treatment is relieving the depressed liver and invigorating spleen to resolve dampness.
Valeriana jatamansi Jones is commonly used herb of miao that can regulate Qi to relieve pain,diminish inflammation to stop diarrhea,dispel wind and dliminate dampness. It can be used in treating stomach and abdominal distension and pain,dyspepsia,diarrhea, dysentery,rheumatism and weakness in lumbar and knee,and so on.Modern research found that valeriana jatamansi Jones have a good therapeutic effect on diseases of the gastrointestinal.Preliminary studies confirmed that through the valeriana jatamansi Jones used in the treatment of IBS has a significant effect,and its technical Powder can improve the gastrointestinal function and the abnormal of nerve and spiritual activity of rat model induced by chronic stress.After the selection of its major components,iridoids plays the most important rold in the gastrointestinal motility hypersplenism and the abnormal of nerve and spiritual activity of the mice,so we can sure the effective part is the Iridoids components.Based on this,We designed a series of experiments to study the treatment and its mechanism of Iridoids composition of Valeriana jatamansi Jones of the IBS animal model.
1 Research on Iridoids composition of Valeriana jatamansi Jones in the role of gastrointestinal function.
1.1 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of normal mice
Methods:Compared with normal group and YJBH group,mice which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 4 days drug given.
Results:Compared with normal group,gastric emptying and small intestinal propulsion in 35.6mg/kg and 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of normal mice.
1.2 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of mice with reserpine
Methods:Compared with normal group,model group and YJBH group,mice with reserpine which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 6 days drug given.
Results:Compared with model group,gastric emptying of 71.2mg/kg group was inhibited,and small intestinal propulsion has no significant change.Gastric emptying and small intestinal propulsion of 35.6mg/kg group were both inhibited.Small intestinal propulsion of 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of mice with reserpine.
1.3 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected AWR and stool quantity in 2 hours.
Results:Compared with model group,pain threshold pressure and Maximum pressure threshold of three Iridoids composition of Valeriana jatamansi Jones groups were all improve,especially the 24.92mg/kg and 12.46mg/kg group(P＜0.001).Stool quantity of 24.92mg/kg and 12.46mg/kg group reduced obviously(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce the visceral sensitivity and the stool quantity of IBS rat model induced by chronic stress.
2 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of spiritual activity function
2.1 Effection of Iridoids composition of Valeriana jatamansi Jones on spiritual activity function of IBS rats induced by chronic stress
Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detect the openfield test score and Sugar water choosed degree.
Compared with model group,the horizontal and vertical motion score of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of lowering,but have no statistically significance.Sugar water choosed degree have no significant change. It means that Iridoids composition of Valeriana jatamansi Jones has central inhibitory action.
2.2 Effection of Iridoids composition of Valeriana jatamansi Jones on weight and food intake of IBS rats induced by chronic stress
Animals were randomly divided into 7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the weight and food intake in 24 hours.
Compared with model group,the rat weight of three Iridoids composition of Valeriana jatamansi Jones groups have no significant change,the food intake of them have a trend of increase,but have no statistically significance.It shows that Iridoids composition of Valeriana jatamansi Jones can improve food intake of IBS rats.
2.3 Effection of Iridoids composition of Valeriana jatamansi Jones on abdominal pain of mice induced by acetic acid
Animals were randomly divided into normal group,Aspirin group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg.0.6%acetic acid was injected into Peritoneal after 6 days drug given.Then we detected Latency of body torsion,0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion.
Compared with model group,Latency of body torsion of 4 ridoids composition of Valeriana jatamansi Jones groups have no significant change.0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion were all obviously increase.It shows that ridoids composition of Valeriana jatamansi Jones can induce abdominal pain caused by acetic acid obviously.
3 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of mechanism of action of rat model induced by chronic stress
3.1 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT and 5-HIAA in colon,serum and central of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the quantity of 5-HT and 5-HIAA in colon,serum and hippocampus by high-pressure liquid method, detected the quantity of 5-HT in amygdale and hypothalamus by immunohistochemistry method.Then we used imag-pro plus analysis software to do Semi-quantitative analysis on area and IOD of Immunostaining positive cells.
Results:Compared with model group,the content of 5-HT and 5-HT/5-HIAA(P＜0.05) in serum of 24.92mg/kg,12.46mg/kg group were ruduced,but the conent of 5-HIAA have no significant change.Three Iridoids composition of Valeriana jatamansi Jones groups can induce the 5-HT content in colon obviously(P＜0.05),and the 24.92mg/kg and 6.23mg/kg group can reduce 5-HT/5-HIAA obviously(P＜0.05),24.92mg/kg group can also reduce 5-HIAA in colon(P＜0.05).24.92mg/kg group can reduce 5-HT/5-HIAA in hippocampus(P＜0.05).Three Iridoids composition of Valeriana jatamansi Jones groups can reduce 5-HT in amygdale and hypothalamus,especially the 12.46mg/kg group(P＜0.01).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce 5-HT content in colon,serum,amygdale and hypothalamus of IBS rat induced by chronic stress.
3.2 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT3R mRNA expression of IBS rats induced by chronic stress
Methods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the 5-HT3R mRNA expression by RT-PCR.
Results:Compared with model group,5-HT3R mRNA expression of Iridoids composition of Valeriana jatamansi Jones group inhibited.It means that it can inhibite the 5-HT3A receptor expression in IBS rat model.It is speculated that this components feedback adjusting the this receptor's expression through receptor-binding with 5-HT3A receptor.
3.3 Effection of Iridoids composition of Valeriana jatamansi Jones on THP1 mRNA expression of IBS rats induced by chronic stress
Methods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the THP1 mRNA expression by RT-PCR.
Results:Compared with model group,all groups have no significant change.It may means that Iridoids composition of Valeriana jatamansi Jones doesn't regulate the TPH1 transcription expression.
3.4 Effection of Iridoids composition of Valeriana jatamansi Jones on SP and VIP of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the content of SP and VIP in plasma and colon.
Results:Compared with model group,the content of SP and VIP in plasma of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce, especially the 24.92mg/kg group(P＜0.05).The VIP content in colon of these three groups have a trend of reduce,especially the 12.46mg/kg and 6.23mg/kg group(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can may improve the IBS symptoms by regulating the SP and VIP content.
3.5 Effection of Iridoids composition of Valeriana jatamansi Jones on mast cell of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then take the colon 3cm away from the anus,using toluidine blue staining method,and count the number of mast cells by low magnification microscope.
Results:Compared with model group,the mast cell number of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce,but the result have no statistically significance.It means Iridoids composition of Valeriana jatamansi Jones may reduce the mast cell number in colon.
Above all,Iridoids composition of Valeriana jatamansi Jones have a significant effect on improving the symptoms of IBS rat model induced by chronic stress,the mechanism may be involved from the colon to the central,including the totally regulated role of 5-HT system,gastrointestinal hormones system and the mast cells immune system.
Our research fixed that Iridoids composition of Valeriana jatamansi Jones was the active ingredient in Valeriana jatamansi Jones treating IBS for the first time.And in-depth investigate its mechanism from neurotransmitter,gastrointestinal hormone and mast cell immune system.Our reaserch lay a solid of theoretical and experimental foundation in exploring our characteristical national new drugs.And it provides the basis of pharmacodynamics for improving clinical standard of 77 version Pharmacopoeia
蜘蛛香是一种常用的苗药,可理气止痛、消炎止泻、祛风除湿。用于脘腹胀痛,消化不良,腹泻,痢疾,风湿痹痛,腰膝酸软等。通过前期研究证实了蜘蛛香应用于治疗IBS有显著疗效,蜘蛛香原粉对慢性应激所致IBS大鼠模型的胃肠功能及精神神经活动的异常均具有改善作用。经过筛选环烯醚萜对小鼠胃肠运动亢进和精神神经活动异常作用最强,故确定有效部位是环烯醚萜。
课题通过观察蜘蛛香环烯醚萜对正常及IBS模型动物的胃肠道功能、精神活动的影响,以及蜘蛛香环烯醚萜干预下IBS大鼠结肠、血清、中枢5-HT含量,结肠5-HTR3A受体的mRNA和色氨酸羟化酶(TPH1)的mRNA表达,结肠和血浆中SP和VIP含量以及结肠中肥大细胞分布,探讨蜘蛛香环烯醚萜对腹泻型IBS的治疗作用及其作用机理,为临床治疗IBS提供实验依据。
1蜘蛛香环烯醚萜对胃肠功能的作用
目的:探讨蜘蛛香环烯醚萜对胃肠功能的影响
1.1蜘蛛香环烯醚萜对正常小鼠胃肠功能的作用
方法:正常小鼠灌胃给予蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg与空白组和越鞠保和丸组对照,给药4日后测定动物的胃排空率和小肠推进率。
结果:蜘蛛香环烯醚萜35.6mg/kg、17.8mg/kg组能减缓胃排空和小肠推作用(P<0.05),说明蜘蛛香环烯醚萜对正常小鼠胃肠功能有一定的抑制作用。
1.2蜘蛛香环烯醚萜对利血平化小鼠胃肠功能的作用
方法:小鼠每日腹腔注射利血平造模,同时灌胃给予蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg与空白组、模型组和越鞠保和丸组对照,给药6日后测定动物的胃排空率和小肠推进率。
结果:腹腔注射利血平后,与正常组比较,模型组小肠推进率增高(P<0.05)。与模型组相比,蜘蛛香环烯醚萜71.2mg/kg组可减缓胃排空(P<0.05),小肠推进没有明显差异。蜘蛛香环烯醚萜35.6mg/kg组可减缓胃排空和小肠推进(P<0.05);蜘蛛香环烯醚萜17.8mg/kg组可减缓小肠推进(P<0.05),胃排空没有明显差异。说明蜘蛛香环烯醚萜可改善利血平导致的胃肠运动亢进。
1.3蜘蛛香环烯醚萜对慢性应激所致IBS大鼠胃肠功能的作用
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。进行慢性应激实验:对照组14-15只/笼,不给任何刺激,其余各组每笼一只孤养,并加以慢性不可预见性的刺激,造模28天,造模期间同时给药。检测各组动物腹部回撤反射压力阈值和2h内排便粒数。
结果:造模后,模型组动物疼痛压力阈值与最大耐受压力阈值均明显降低(P<0.01),表明动物内脏敏感性增高,同时动物排便量明显增多(P<0.01)。蜘蛛香环烯醚萜各给药组动物与模型组比较,疼痛压力阈值与最大耐受压力阈值均增加,其中蜘蛛香环烯醚萜24.92mg/kg组和12.46mg/kg组作用极显著(P<0.001)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组动物排便粒数显著减少,与模型组相比有显著差异(P<0.05)。表明蜘蛛香环烯醚萜可改善应激所致IBS大鼠模型的胃肠功能,降低内脏敏感性,减少排便数。
结论:IBS是一种胃肠紊乱性疾病,临床表现为腹痛、腹泻或者便秘等消化道症状,症状持续存在或间歇发作。蜘蛛香环烯醚萜可以减缓正常小鼠的胃肠运动和利血平化小鼠的胃肠功能亢进,降低慢性应激所致IBS模型大鼠的内脏敏感性,显著减少了IBS模型大鼠的排便数量,从而改善腹泻型IBS的临床症状。
2蜘蛛香环烯醚萜对神经系统功能的影响
目的:探讨蜘蛛香环烯醚萜对精神活动的影响
2.1蜘蛛香环烯醚萜对慢性应激所致IBS大鼠精神活动的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。检测各组动物敞箱试验得分和糖水偏嗜度。
结果:蜘蛛香环烯醚萜各给药组动物与模型组相比,敞箱试验水平运动得分与垂直运动得分增加,蔗糖偏嗜度提高。
2.2蜘蛛香环烯醚萜对醋酸所致小鼠疼痛的影响
方法:小鼠随机分为对照组、蜘蛛香环烯醚萜71.2mg/kg、35.6mg/kg、17.8mg/kg、8.9mg/kg组、阿司匹林组。给药6日后腹腔注射0.6%醋酸,观察扭体潜伏期,前10min扭体次数,后10min扭体次数,总共20min扭体次数。
结果:与对照组相比,蜘蛛香环烯醚萜各给药组扭体潜伏期无明显变化,前10min扭体次数,后10min扭体次数,总共20min扭体次数均明显减少(P<0.01)。表明蜘蛛香环烯醚萜对化学刺激所致疼痛,有显著的镇痛作用。
结论:蜘蛛香为缬草属植物,现代药理研究发现其有很好的镇静催眠和抗焦虑抗抑郁作用。本实验研究发现蜘蛛香环烯醚萜通过增强慢性应激所致的IBS模型大鼠的活动能力和兴趣缺失,降低摄食量,对精神活动有一定的改善作用。同时,蜘蛛香环烯醚萜可显著降低醋酸所致小鼠的扭体次数,说明其有良好的镇痛作用。
3蜘蛛香环烯醚萜治疗肠易激综合征机理
3.1蜘蛛香环烯醚萜对5-HT神经递质的影响
3.1.1蜘蛛香环烯醚萜对外周和中枢5-HT含量的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠结肠、血清和脑中5HT、5-HIAA的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取血清、结肠和下丘脑以高压液相法检测5-HT和5-HIAA含量,取脑以免疫组化法观察海马和杏仁核5-HT含量,并用imag-pro plus图像分析软件对5-HT免疫染色阳性细胞面积(Area)、积分光密度(IOD)进行半定量分析。
结果:对结肠5-HT的影响造模后,模型组动物结肠中5-HT含量明显增加,5-HIAA含量及5-HT/5-HIAA比值无明显变化。蜘蛛香环烯醚萜各组均可明显降低结肠中5-HT的含量(P<0.05),24.92mg/kg组和6.23mg/kg可显著降低5-HT/5-HIAA比值(P<0.05),24.92mg/kg可明显降低结肠中5-HIAA的含量(P<0.05)。
对血清5-HT的影响造模后,模型组动物血清中5-HT含量明显增加(P<0.01),5-HIAA含量无明显变化,5-HT/5-HIAA比值增加(P<0.05)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组可降低血清中5-HT的含量及5-HT/5-HIAA比值(P<0.05),但5-HIAA含量无明显变化。
对下丘脑5-HT的影响模型组动物下丘脑中5-HT含量明显下降(P<0.05),5-HIAA及5-HT/5-HIAA变化不明显。蜘蛛香12.46mg/kg、6.23mg/kg剂量组可明显升高5-HT(P<0.05),但5-HT/5-HIAA没有明显变化。
对海马和杏仁核5-HT的影响造模后,模型组大鼠阳性细胞面积和积分光密度降低(P<0.05)。蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组较模型组有明显上升(P<0.05)。
以上结果表明蜘蛛香环烯醚萜可以降低外周IBS模型大鼠结肠、血清的5-HT含量,可升高中枢下丘脑、海马及杏仁核中的5-HT含量。
3.1.2蜘蛛香环烯醚萜对大鼠5-HT合成限速酶的影响
目的:蜘蛛香环烯醚萜对慢性应激所致IBS大鼠色氨酸羟化酶mRNA表达的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取动物肛门上方3cm处结肠,以RT-PCR方法检测各组及蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组结肠的TPH1表达。
结果:造模后,模型组和各用药组之间TPH1 mRNA水平差异不显著。表明蜘蛛香环烯醚萜不影响色氨酸羟化酶的转录表达。
3.1.3蜘蛛香环烯醚萜对5-HT受体的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠5-HT3受体mRNA表达的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组,除对照组外,其余各组进行慢性应激实验。取动物肛门上方3cm处结肠,以RT-PCR方法检测各组及蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg组结肠的mRNA表达。
结果:造模后,模型组的5-HTR3A/β-Actin比值明显高于对照组,说明慢性应激可引起大鼠结肠的5-HTR3A表达上调;蜘蛛香环烯醚萜组与模型组相比,5-HTR3A/β-Actin比值显著降低,5-HTR3A受体表达水平发生了相应下调。表明蜘蛛香环烯醚萜可抑制5-HT3A受体的转录。
结论:蜘蛛香环烯醚萜通过降低结肠、血清中5-HT含量,下调结肠5-HTR3A受体表达水平改善IBS胃肠道症状;其对5-HT含量的影响不是通过抑制色氨酸羟化酶实现的。造模后,中枢5-HT呈现降低趋势,这可能是导致动物出现活动能力下降和兴趣缺失的原因之一,蜘蛛香环烯醚萜可以增加下丘脑、海马和杏仁核中5-HT含量,推断蜘蛛香环烯醚萜可通过干预中枢的5-HT通路来改善IBS精神症状。
3.2蜘蛛香环烯醚萜对胃肠激素的影响
目的:探讨蜘蛛香环烯醚萜对慢性应激所致IBS大鼠SP和VIP的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。除对照组外,其余各组进行慢性应激实验。以放免法检测动物结肠和血浆中SP和VIP含量。
结果:对结肠SP和VIP的影响造模后,模型组结肠中SP有升高趋势,VIP有降低趋势,但均无统计学意义。蜘蛛香环烯醚萜各剂量组结肠中SP较模型组有降低趋势,VIP则有升高趋势,可降低SP/VIP值。
对血浆SP和VIP的影响造模后,模型组大鼠血浆中SP和VIP均上升,其中VIP上升明显(P<0.05)。蜘蛛香环烯醚萜各组对血浆中SP和VIP有下降趋势,其中24.92mg/kg组较模型组下降明显(P<0.05),6.23mg/kg组SP下降显著(P<0.05)。
结论:蜘蛛香环烯醚萜可能通过降低结肠和血浆中SP含量,降低结肠SP/VIP值,降低内脏敏感性,改善胃肠功能亢进所出现的症状。
3.3蜘蛛香环烯醚萜对免疫系统的影响
目的:蜘蛛香环烯醚萜对慢性应激所致IBS大鼠肥大细胞的影响
方法:动物随机分为对照组、模型组、昂丹司琼组、氟西汀组、蜘蛛香环烯醚萜24.92mg/kg、12.46mg/kg、6.23mg/kg组。除对照组外,其余各组进行慢性应激实验。取距肛门3cm处的结肠行甲苯胺蓝染色,以低倍显微镜观察肥大细胞分布。
结果:造模后,模型组较对照组肥大细胞明显增多,与模型组比较,蜘蛛香环烯醚萜各组结肠粘膜固有层及粘膜下层血管周围肥大细胞数量减少。表明蜘蛛香环烯醚萜可能减少结肠中肥大细胞数量。
结论:蜘蛛香环烯醚萜可能通过降低肥大细胞渗出,调节免疫系统状态参与IBS的治疗。
综上所述,蜘蛛香环烯醚萜可以抑制胃肠功能亢进,降低内脏敏感性,改善精神状态,并具有良好的镇痛作用,从而改善腹泻型IBS的临床症状。其机制可能涉及了蜘蛛香环烯醚萜对外周和中枢的5-HT系统、胃肠激素系统及肥大细胞免疫系统的调节作用。
课题首次确定了蜘蛛香治疗IBS的有效部位为环烯醚萜类成分,并对其作用机制从神经递质,胃肠激素及免疫系统等不同方面进行了研究,为发掘具有我国民族特色的药用资源,深入探讨其物质基础和作用机理提供了科学依据。
Irritable bowel syndrome is one of the disorders of gastrointestinal function,with the characteristic of abdominal pain or discomfort,associated with characters change and habit change in stool.Epidemiological survey shows that the rate of this disease is as high as 10%to 20%in healthy people,accounting for more than 50%of the number of patients coming to the digestion department.Its basis of pathophysiology is mainly based on the abnormal of gastrointestinal kinetics and the increased visceral sensitivity,but the specific mechanism is not clear.The Chinese medicine attributed the irritable bowel syndrome to the scope of "intestinal depression",that the pathogenesis are most the liver depression and spleen deficiency and uncoordination of qi and blood,the main treatment is relieving the depressed liver and invigorating spleen to resolve dampness.
Valeriana jatamansi Jones is commonly used herb of miao that can regulate Qi to relieve pain,diminish inflammation to stop diarrhea,dispel wind and dliminate dampness. It can be used in treating stomach and abdominal distension and pain,dyspepsia,diarrhea, dysentery,rheumatism and weakness in lumbar and knee,and so on.Modern research found that valeriana jatamansi Jones have a good therapeutic effect on diseases of the gastrointestinal.Preliminary studies confirmed that through the valeriana jatamansi Jones used in the treatment of IBS has a significant effect,and its technical Powder can improve the gastrointestinal function and the abnormal of nerve and spiritual activity of rat model induced by chronic stress.After the selection of its major components,iridoids plays the most important rold in the gastrointestinal motility hypersplenism and the abnormal of nerve and spiritual activity of the mice,so we can sure the effective part is the Iridoids components.Based on this,We designed a series of experiments to study the treatment and its mechanism of Iridoids composition of Valeriana jatamansi Jones of the IBS animal model.
1 Research on Iridoids composition of Valeriana jatamansi Jones in the role of gastrointestinal function.
1.1 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of normal mice
Methods:Compared with normal group and YJBH group,mice which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 4 days drug given.
Results:Compared with normal group,gastric emptying and small intestinal propulsion in 35.6mg/kg and 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of normal mice.
1.2 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of mice with reserpine
Methods:Compared with normal group,model group and YJBH group,mice with reserpine which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 6 days drug given.
Results:Compared with model group,gastric emptying of 71.2mg/kg group was inhibited,and small intestinal propulsion has no significant change.Gastric emptying and small intestinal propulsion of 35.6mg/kg group were both inhibited.Small intestinal propulsion of 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of mice with reserpine.
1.3 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected AWR and stool quantity in 2 hours.
Results:Compared with model group,pain threshold pressure and Maximum pressure threshold of three Iridoids composition of Valeriana jatamansi Jones groups were all improve,especially the 24.92mg/kg and 12.46mg/kg group(P＜0.001).Stool quantity of 24.92mg/kg and 12.46mg/kg group reduced obviously(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce the visceral sensitivity and the stool quantity of IBS rat model induced by chronic stress.
2 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of spiritual activity function
2.1 Effection of Iridoids composition of Valeriana jatamansi Jones on spiritual activity function of IBS rats induced by chronic stress
Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detect the openfield test score and Sugar water choosed degree.
Compared with model group,the horizontal and vertical motion score of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of lowering,but have no statistically significance.Sugar water choosed degree have no significant change. It means that Iridoids composition of Valeriana jatamansi Jones has central inhibitory action.
2.2 Effection of Iridoids composition of Valeriana jatamansi Jones on weight and food intake of IBS rats induced by chronic stress
Animals were randomly divided into 7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the weight and food intake in 24 hours.
Compared with model group,the rat weight of three Iridoids composition of Valeriana jatamansi Jones groups have no significant change,the food intake of them have a trend of increase,but have no statistically significance.It shows that Iridoids composition of Valeriana jatamansi Jones can improve food intake of IBS rats.
2.3 Effection of Iridoids composition of Valeriana jatamansi Jones on abdominal pain of mice induced by acetic acid
Animals were randomly divided into normal group,Aspirin group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg.0.6%acetic acid was injected into Peritoneal after 6 days drug given.Then we detected Latency of body torsion,0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion.
Compared with model group,Latency of body torsion of 4 ridoids composition of Valeriana jatamansi Jones groups have no significant change.0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion were all obviously increase.It shows that ridoids composition of Valeriana jatamansi Jones can induce abdominal pain caused by acetic acid obviously.
3 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of mechanism of action of rat model induced by chronic stress
3.1 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT and 5-HIAA in colon,serum and central of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the quantity of 5-HT and 5-HIAA in colon,serum and hippocampus by high-pressure liquid method, detected the quantity of 5-HT in amygdale and hypothalamus by immunohistochemistry method.Then we used imag-pro plus analysis software to do Semi-quantitative analysis on area and IOD of Immunostaining positive cells.
Results:Compared with model group,the content of 5-HT and 5-HT/5-HIAA(P＜0.05) in serum of 24.92mg/kg,12.46mg/kg group were ruduced,but the conent of 5-HIAA have no significant change.Three Iridoids composition of Valeriana jatamansi Jones groups can induce the 5-HT content in colon obviously(P＜0.05),and the 24.92mg/kg and 6.23mg/kg group can reduce 5-HT/5-HIAA obviously(P＜0.05),24.92mg/kg group can also reduce 5-HIAA in colon(P＜0.05).24.92mg/kg group can reduce 5-HT/5-HIAA in hippocampus(P＜0.05).Three Iridoids composition of Valeriana jatamansi Jones groups can reduce 5-HT in amygdale and hypothalamus,especially the 12.46mg/kg group(P＜0.01).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce 5-HT content in colon,serum,amygdale and hypothalamus of IBS rat induced by chronic stress.
3.2 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT3R mRNA expression of IBS rats induced by chronic stress
Methods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the 5-HT3R mRNA expression by RT-PCR.
Results:Compared with model group,5-HT3R mRNA expression of Iridoids composition of Valeriana jatamansi Jones group inhibited.It means that it can inhibite the 5-HT3A receptor expression in IBS rat model.It is speculated that this components feedback adjusting the this receptor's expression through receptor-binding with 5-HT3A receptor.
3.3 Effection of Iridoids composition of Valeriana jatamansi Jones on THP1 mRNA expression of IBS rats induced by chronic stress
Methods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the THP1 mRNA expression by RT-PCR.
Results:Compared with model group,all groups have no significant change.It may means that Iridoids composition of Valeriana jatamansi Jones doesn't regulate the TPH1 transcription expression.
3.4 Effection of Iridoids composition of Valeriana jatamansi Jones on SP and VIP of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the content of SP and VIP in plasma and colon.
Results:Compared with model group,the content of SP and VIP in plasma of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce, especially the 24.92mg/kg group(P＜0.05).The VIP content in colon of these three groups have a trend of reduce,especially the 12.46mg/kg and 6.23mg/kg group(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can may improve the IBS symptoms by regulating the SP and VIP content.
3.5 Effection of Iridoids composition of Valeriana jatamansi Jones on mast cell of IBS rats induced by chronic stress
Methods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then take the colon 3cm away from the anus,using toluidine blue staining method,and count the number of mast cells by low magnification microscope.
Results:Compared with model group,the mast cell number of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce,but the result have no statistically significance.It means Iridoids composition of Valeriana jatamansi Jones may reduce the mast cell number in colon.
Above all,Iridoids composition of Valeriana jatamansi Jones have a significant effect on improving the symptoms of IBS rat model induced by chronic stress,the mechanism may be involved from the colon to the central,including the totally regulated role of 5-HT system,gastrointestinal hormones system and the mast cells immune system.
Our research fixed that Iridoids composition of Valeriana jatamansi Jones was the active ingredient in Valeriana jatamansi Jones treating IBS for the first time.And in-depth investigate its mechanism from neurotransmitter,gastrointestinal hormone and mast cell immune system.Our reaserch lay a solid of theoretical and experimental foundation in exploring our characteristical national new drugs.And it provides the basis of pharmacodynamics for improving clinical standard of 77 version Pharmacopoeia
引文
[1]Neal KR,Hebden J,Spiller R.Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome:postal survey of patients.BMJ,1997,314:779-782
[2]刘方,王承党.肠道感染和肠道菌群鱼肠易激综合征.国际消化病杂志,2008,28(1):23-25
[3]Vergrnolle N,Renaux B,Hollenberg MD,et al.Role of rat mast cell protease-2 in intestinal transport and barrier function.Gast roenterology,1998,114(suppl):A674
[4]Van der Waaji D.History of recognition and measurement of colonization resistance of the digestive tract as an introduction to selective gastrointestinal decontamination.Epidemiol Infec,1992,109:315-326
[5]刘俊康,闫国华,章荣华,等.细菌潜生体与IBS关系的初步研究.第三军医大学学报,2007,29(4):321-323
[6]Cruz Ruiz MA,Ortiz Herrera RB.Muniz Jurado D.et al.Association of depression and anxiety in patients with irritable bowel syndrome(Article in Spanish).Rev Gastroenterol Mex,2007,72(1):29-33.
[7]高保华,刘长宁.肠易激综合征的心理社会因素研究.中国社区医师,2007,9(6):25
[8]陈钟鸣,高小燕,黄六英,等.肠易激综合征患者焦虑抑郁评价报告.实用临床医学,2008,9950;44-46
[9]Locke GR,Zinsmeister AR,Talley N J et al.Familial association in adults with functional gastrointestinal disorders[J].Mayo Clin Proc,2000,75(9):907-912
[10]Levy RL,Jones KR,Whitehead WE,et al.Irritable bowel syndrome in twins heredity and social learning both contribute to etiology[J].Gastroentero,2001,121(4):799-804
[11]Houghton LA,Jackson NA,Whorwhell P J,et al.Do male sex hormones protect from irritable bowel syndrome?[J].Am J Gastroentero J.2000,95(9):2296-2300
[12]孔庆建,张辉,孙波,等.肠易激综合征的病因与发病机制.中国煤炭工业医学杂志.2006,9(10):1033-1034
[13]游元明,刘劲松.肠易激综合征感觉异常研究进展.国际消化病杂 志.2007,27(3):167-169
[14]詹丽杏,许国铭,李兆申,等.肠易激综合征患者活动期和缓解期血浆5-羟色胺、5-羟吲哚乙酸的变化.第二军医大学学报,2003,24(2):152-154
[15]Delgado M,Pozo D,Ganea D.The Significance of vasoactive intestinal peptide in immunomodulation.Pharmacol Rev,2004,56(2):249-290
[16]陈晓敏,张燕华,毛峻岭,等.肠易激综合征患者结肠粘膜P物质、血管活性肠肽和肥大细胞的变化.胃肠病学,2008,13(4):228-230
[17]宋继中,王巧民,丁西平,等.肠易激综合征患者结肠粘膜神经肽和IL-1β变化及其意义.胃肠病学和肝病学杂志.2007,16(3):219-222
[18]梁荣新,郑琴芳,梁列新,等.肠易激综合征与胃肠激素的关系.中国综合临床,2004,20(8):702-703
[19]王伟岸,钱家鸣,潘国宗.结肠粘膜肥大细胞活化在肠易激综合征发病中的作用.中华消化杂志.2003,23(5):263-266
[20]董文珠,邹多武,李兆申,等.肠易激综合征患者内脏高敏感性的机制研究.中华消化杂志,2004,24(1):18-22
[21]郭敏,李延青,刘传勇,等.肠易激综合征大鼠模型外周血免疫调节性T细胞的研究.山东大学学报(医学版).2006,44(5):514-518
[22]张海燕,吴萍,李延青,等.肠易激综合征患者的免疫学机制探讨.胃肠病学和肝病学杂志.2006,15(3):285-287
[23]Charles DRM,Joanna F,Laura R,et al.Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome.Gastroenterology.2004,127(6):1695-1703
[1]周福生,廖荣鑫.肠易激综合征中西医诊断与治疗.北京:中国医药科技出版社.2007:40
[2]时乐,卜平,郑新梅,等.211例肠易激综合征证候病机的研究.中医研 究,2005,18(11):24-26
[3]梅武轩.肠易激综合征的中医辨治经验.辽宁中医学院学报,2005,7(5):444-445.
[4]钟海平.通肠舒痛饮治疗便秘型肠易激综合征97例.实用中医药杂志,2006,22(5):276-277
[5]崔莉红.从脾论治腹泻型肠易激综合征.陕西中医,2008,29(1):46-47
[6]章力勤.健脾化湿汤治疗肠易激综合征30例临床观察.浙江中医药大学学报,2006,30(3):245-246
[7]王金雁.痛泻要方合参苓白术散加减治疗腹泻型肠易激综合征50例.山西中医,2008,24(6):13-14
[8]陶云,董明霞,寇焰,等.疏肝健脾法治疗腹泻型肠易激综合征体会.北京中医,2006,25(8):458-460
[9]刘力,沈舒文.肠易激综合征中医辨证论治.实用中医内科杂志,2002,16(3):157-158
[10]苏佩仪.疏肝补脾健胃法治疗肠易激综合征96例疗效观察.河北中医,2004,26(5):345
[11]周福生,吴文江,张庆宏.胃肠功能性疾病证型分布的统计分析.中华国际医学杂志,2002,2(5):438,442
[12]吴成胜,苏良.从肝脾论治腹泻型肠易激综合征探微.山东中医药大学学报,2004,28(1):25-26
[13]李炜.辨证治疗肠易激综合征39例.山西中医,2004,20(5):17-18
[14]王庆成.辨证治疗肠易激综合征56例.河南中医,2004,24(4):32-33
[15]赵爱莲.辨证分型治疗肠易激综合征172例.江西中医药,2006,5:28-29
[16]范汉淮.辨证分型治疗腹泻型肠易激综合征40例.辽宁中医学院学报,2006,8(1):47-48
[17]孙长清,李联社.理气健脾汤治疗肠易激综合征160例.陕西中医,2008,29(2):189-190
[18]许慧玲,尹俊芳,叶松.自拟固肠汤治疗腹泻型肠易激综合征45例临床观察.山西中医学院学报,2008,9(2):33-34
[19]王金雁.痛泻要方合参苓白术散加减治疗腹泻型肠易激综合征50例.山西中医,2008,24(6):13-14
[20]张蜀,吴至久,廖伯年.逍遥散加味治疗便秘型肠易激综合征27例.实用中医内科杂志.2008,22(3):31
[21]王长来.养血通腑汤治疗便秘型肠易激综合征50例.江西中医药,2008,39(303):21
[22]高强,李慧臻.宣肺理气活血法治疗便秘型肠易激综合征38例.吉林中医药,2007,27(12):25-26
[23]武雪宇.辨证施针治疗肠易激综合征31例.上海针灸杂志,2006,25(6):25-26
[24]杨国梁,胡淑宏.中药合艾灸治疗肠易激综合征40例临床观察.针灸临床杂志,2004,20(7):13
[25]陈国源,梁萌,许树根,等.肠易激综合征中药配合穴位注射与心理治疗82例.中国中西医结合消化杂志,2006,14(2):124-125
[26]谢胜,张志杰,梁谊深.中草药蒸汽疗法合指针治疗肠易激综合征64例.陕西中医,2006,27(1):54-55
[27]陈春永,郑永臻,朱迪盈.健脾补肾中药联合培菲康治疗腹泻型肠易激综合征44例.世界中医药,2008,3(3):163
[28]董晓明.中西医结合治疗腹泻型肠易激综合征60例.中国中西医结合消化杂志,2006,14(6):410-411
[29]华军.中西医结合治疗肠易激综合征40例.中国中西医结合消化杂志,2006,14(1):53-54
[30]蓝惠玲,刘友章,李耿成,等.加味痛泻要方颗粒治疗腹泻型肠易激综合征42例疗效观察.新中医,2005,37(5):26-27
[31]彭慕斌,田英.复方黄连素片治疗肝郁脾虚型肠易激综合征48例.职业与健康,2005,21(12):2040-2041
[32]谢建群,潘相学.健脾温中法对脾胃虚寒型肠易激综合征模型大鼠生长抑素的影响.中医杂志,2004,45(9):697-699
[33]谢建群,郑昱,吴大正,等.疏肝饮对腹泻型肠易激综合征大鼠血管活性肠肽和P物质的影响.上海中医药大学学报,2004,18(3):36-39
[34]王海云,石君杰.宁肠汤治疗大鼠肠易激综合征的实验研究.中国中医药科技,2003,10(5):266-269
[35]王海云,石君杰,李新伟.宁肠汤对肠易激综合征大鼠下丘脑-垂体-肾上腺轴干预作用的研究.中国中医药科技,2006,13(6):393-394
[36]石君杰.宁肠汤对肠易激综合征大鼠炎性细胞因子影响的实验研究.中国中医药科技,2008,15(2):103-104
[37]周福生,吴文江,黄志新.顺激合剂对肠易激综合征患者结肠动力学影响的研究.中医杂志,2004,45(11):856-858
[38]沈骏,诸琦,袁耀宗,等.肠吉安口服液对肝脾不和腹泻型肠易激综合征患者大脑功能区激活面积的影响.中国中西医结合消化杂志,2005,13(4):218-222
[39]霍清萍,张仲伟,王兵,等.调肝运脾方对腹泻型肠易激综合征患者脑内兴奋区域活动的影响.上海中医药杂志,2007,41(11):40-43
[40]占宏伟,项康柏,陈芝芸,等.肠易激综合征不同中医证型前列腺素E_2和环核苷酸的变化及意义.浙江中医学院学报,2000,24(3):16-18
[41]陈芝芸,严茂祥,项柏康.肠易激综合征中医证型与胃肠激素关系的探讨.中国中西医结合杂志,2002,22(9):664-666
[1]Coutinho S,Plotsky PM,Sablad M,et al.Neonatal maternal separation alters stress-induced response to viscerosomatic nociceptive stimuli in rats.Am J Physiol Gastrointest Liver Physio,2002,282:307-316
[2]Williams CL,Villar RG,Peterson JM,et al.Stress-induced changes in intestinal transit in the rats-A model for irritable bowel syndrome.Gastroenterology,1988,94;611-621
[3]李延青,杨云生,陈建.肠易激综合征.北京:中国医药科技出版社.2005:94
[4]Tache Y,Garrick T,Raybouid H.Central nervous system action of peptides to infulence gastrointestinal motor function.Gastroenterology,1990,98(2):517-518
[5]collions SM,McHugh K,Jacobson K,et al.Previous inflammation alters the response of the rat colon to stress.Gastroenterology.1996 Dec,111(6):1509-1515
[6]Al-Chaer ED,Kawasaki M,Pasricha PJ.A new model of chronic visceral hypersensitivity in adult rats incluced by colon irritation during postnatal development.Gastroenterology,2000,119(5):1276-1285
[7]Scott RB,Tan DT,Miampamba M,et al.Anaphy-laxis-induced alterations in intestinal motility:role of extrimsic neural pathways.Am-J-Physiol,1998,275(4 Pt 1):G812-821
[8]胡萍萍,吕宾,范一宏.内脏高敏感大鼠脑部5-羟色胺表达差异的研究.中华消化杂志,2006,26(5):347-348
[9]Ness TJ,Gebhart GF.Colorectal distension as a noxious visceral stimulus:physiologic and phar,,,logic characterization of pseudaffective refle,,,in the rat.Brain Res,1988(4),450:153-169
[1O]Chen JJ,Li Z,Pan H,etal.Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter abnormal intestinal motility and the expression of cation transporters.J Neurosci,2001,21:6348-6361
[11]彭丽华,杨云生,孙刚,等.便秘型肠易激综合征新概念模型的建立.世界华人消化杂志,2004,12(1):112-116
[12]徐俊荣,罗金燕.肠易激综合征动物模型研究进展.基础医学与临床.2006,26(8):902-904
[13]Naliboff BD,Chang L,Munakata J,et al.Towards an integrative model of irritable bowel syndrome.Prog Brain Res,2000,122:413-423
[1]Chen JX,Pan H,Rothman TP,et al.Guinea pig 5-HT transporter:Cloning,expression,distribution and function in intestinal sensory reception.Am J Physiol,1998;275:G433-G448
[2]Gershon MD,Tack J(2007) The serotonin signaling system:from basic understanding to drug development for functional GI disorders.Gastroenterol,2007,132:397-414
[3]詹丽杏,许国铭,李兆申,等.肠易激综合征患者活动期和缓解期血浆5-HT、5-HIAA的变化.第二军医大学学报,2003,24(2):152-154
[4]Gershon MD.Review article:serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motility.Aliment Pharmacol Ther 20(Suppl7):3-14
[5]Pan H,Gershon MD.Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine.J Neurosci 20:3295-3309
[6]Grider JR.Neurotransmitters mediating the intestinal peristaltic reflex in the mouse.J Pharmacol Exp Ther 307:460-467
[7]迟燕,刘新光,李江.5-羟色胺4受体在调解应激大鼠内脏敏感性中的作用.中华消化杂志,2003,24(9):533-536
[8]丁斐,神经生物学.北京:科学出版社.2007:174-175
[9]孙凤艳.医学神经生物学.上海:上海科学技术出版社.2008:148
[10]陈钟鸣,高小燕,黄六英,等.肠易激综合征患者焦虑抑郁评价报告.实用临床医学,2008,9950;44-46
[11]Ringel Y,Drossman DA,Turkington TG,et al.Dysfunctions of the motivational affective pain system inpatients with IBS:PET brain imaging in response to rectal ballon distention.Gastroenterology,2000(suppl):A474
[12]胡萍萍,吕宾,范一宏.内脏高敏感大鼠脑部5-羟色胺表达差异的研究.中华消化杂志,2006,26(5):347-348
[13]孙刚,杨云生,彭丽华,等.肠易激综合征大鼠内脏敏感性异常与结肠及中枢神经系统5-HT和c-fos表达的关系.胃肠病学和肝病学杂志.2008,17(4):313-317
[14]Hartig PR,Hoyer D,Humphrey PP,et al.Alignment of receptor nomenclature with the human genome classification of 5-HT1B and 5-HT1D receptor subtypes.Trends Pharmacol Sci,1996,17:1003-1005
[15]Hoyer,D,Hannon JP,Martin GR.Molecular,pharmacological and functional diversity of 5-HT receptors.Pharmacol Biochem Behav,2002,71:533-554
[16]Sanger GJ,Andrews PLR.Treatment of nausea and vomiting:gaps in our knowledge.Autonom Neurosci Basic Clin,2006,129:3-16
[17]Davies PA,Pistis M,Hanna MC,et al.The 5-HT3B subunit is a major determinant of serotonin-receptor function.Nature,1999,397:359-363
[18]Niesler B,Frank B,Kapeller J,et al.Cloning,physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C,HTR3D and HTR3E.Gene,2003,310:101-111
[19]Glatzle J,Stemini C,Robin C,et al.Expression of 5-HT3 receptors in the rat gastrointestinal tract.Gastroenterology,2002,123:217-226
[20]Raybould HE,Glatzle J,Robin C,et al.Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying.Am J Physiol,2003,284:G367-G372
[21]王静,5-羟色胺受体及转运体在肠易激综合征发病机制中的作用.上海交通大学学报(医学版),2008,26(8):1051-1054
[22]Bender E,Pindon A,Van Oers I,et al.Structure of the human serotonin 5-HT4receptor gene and cloning of a novel 5-HT4 splice variant.J Neurochem,2000,74:478-489
[23]Galligan JJ,LePard KJ,Schneider DA,et al.Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system.J Auton Nerv Syst,2000,81:97-103
[24]Wouters MM,Farrugia G,Schemann M.5-HT receptors on interstitial cells of Cajal,smooth muscle and enteric nerves.Neurogastroenterol Motil 2007,19(Suppl 2):5-12
[25]Clayton NM,Sargent R,Butler A,et al.The pharmacological properties of the novel selective 5-HT3 receptor antagonist,alosetron,and its effects on normal and perturbed small intestinal transit in the fasted rat.Neurogastroenterol Motil,1999
[26]Mori T,Kawano K,Shishikura T.5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats.J Pharmacol Sci,2004,94:73-7
[27]Gershon MD,Tack J.The serotonin signaling system:from basic understanding to drug development for functional GI disorders.Gastroenterol,2007,132:397-414
[28]Berman SM,Chang L,Suyenobu B,et al.Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist alosetron.Gastroenterology,2002,123:969-977
[29]Bradesi S,Lao L,McLean PG,et al.Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia.Pain,2007,130:56-65
[30]Kaumann AJ,Levy FO.5-hydroxytryptamine receptors in the human cardiovascular system.Pharmacol Ther,2006,111:674-706
[31]林懋惺,杨丽.5-羟色胺受体与肠易激综合征.医学综述,2007,13(5):398-400
[32]Baker DE.Rationale for USing serotonergic agents to treat irritable bowel syndrome.Am J Health-Syst Pharm,2005,62:700-711
[33]Gershon MD.Nerves,reflexes,and the enteric nervous system.J Clin Gastroentero1,2005,39:S184-S193
[34]Galligan JJ,Pan H,Messori E.Signalling mechanism Coupled to 5-hydfoxytryptamine4 receptor-mediated facilitation of fast synaptic transmission in the guinea pig ileum myenteric plexus.Neurogastroenterol Motil,2003,15:523-529
[35]Taniyama K,Makimoto N,Furuichi A,et a1.Functions of peripheral 5-hydfoxytryptamine receptors,especially 5-hydroxytryptamine4 receptor,in gastrointestinal motility.J Gastroenterol,2000,35:575-582
[36]Cellek S,John AK,Thangiah R,et al.5-HT4 receptor agonists enhance both cholineric and nitrergic actiVities in human isolated colon circular muscle.Neurogastroenterol Motil,2006,18:853-861
[37]Tam FS,Hillier K,Bunce KT.Characterization of the 5-hydfoxytryptamine receptOr type involved in inhibition of spontaneous actiVity Of human isolated colonic circular muscle.Br J Pharmacol,1994,113:143-150
[38](?) B,(?) M,(?) G.Serotonin increases protective duodenal bicarbonate secretion Via ellteric ganglia and a 5-HT4-dependent pathway.Scand J Gastroenterol,2006,41:1279-1289
[39]BoriBan RA,Burleigh DE.Heterogerieity of 5-HT receptors mediating secretion in the human intestine.Ann NY Acad Sci,1997,812:224-225
[40]Greenwood-Van Meerveld B,Venkova K,et al.ActiVation of peripheral 5-HT receptors attenuates colonic sensitiVity to intraluminal distension.Neurogastroenterol Motil,2006,18:76-86
[41]Sun YN,Luo JY.Effects of tegaserod on Fos,substance P and calcitonin gene-related peptide expressiOn induced by colon innammation in 1umbarsacral spinal cord.World J Gastroenterol,2004,10:1830-1833
[42]Degen L,Petrig C,Studer D,et al.Effect of tegaserod on gut transit in male and female subjects.Neurogastroenterol Motil,2005,17:821-826
[43]王静,5-羟色胺受体及转运体在肠易激综合征发病机制中的作用.上海交通大学学报(医学版),2008,26(8):1051-1054
[44]Camilleri M,Andrews CN,Bharucha AE,et al.Alterations in expression of pll and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome.Gastroenterology,2007,132:17-25
[45]Van Lelyveld N,Ter Linde J,Schipper ME,et al.Regional differences in expression of TPH-1,SERT,5-HT(3) and 5-HT(4) receptors in the human stomach and duodenum.Neurogastroenterol Motil,2007,19:342-34
[46]Coates MD,Mahoney CR,Linden DR,et al.Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology,2004,126:1657-1664
[47]代子艳,王巧民.5-羟色胺转运体基因多态性与肠易激综合征.国际消化杂志,2008,28(5):364-367
[48]Spigset O.Adverse reactions of selective reuptake inhibitors:reports from a spontaneous reporting system.Drug Saf,1999,20:277-287
[49]Coates MD,Johnson AC,Greenwood-Van Meerveld B,et al.Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse.Neurogastroenterol Motil,20016,18:464-471
[50]Chen JJ,Zhishan L,Pan H,et al.Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter(SERT):abnormal intestinal motility and the expression of cation transporters.J Neurosci,2001,21:6348-6361
[51]Talley NJ.Pharmacologic therapy for the irritable bowel syndrome.Am J Gastroenterol,2003,98:750-758
[52]Tack J,Broekaert D,CorsettiM,et al.Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man.Aliment Pharmacol Ther,2006,23:265-274
[53]Kuiken SD,Tytgat GN,Boeckxstaens GE.The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome:a double blind,randomized,placebo-controlled study.Clin Gastroenterol Hepatol,2003,1:219-228
[1]兰茂著.《滇南本草》整理组整理,滇南本草,第二卷,昆明.云南人民出版社.1977.273
[2]李时珍.本草纲目,第二册.北京:人民卫生出版社,1979:845
[3]中华人民共和国卫生部药典委员会编.中华人民共和国药典,1977年版,一部.北京:人民卫生出版社,1978:633
[4]吴家荣.中草药蜘蛛香(印度缬草)的鉴定研究.新医药通讯,1976,1:73-78
[5]郭济贤,等.缬草类专题研究.《常用中药材品种整理和质量研究》第二册,福建科学技术出版社,1997:490
[6]刘娟,等.缬草属药用植物的研究进展.黑龙江医药科学,2007,(30)1:94-95
[7]王宗玉,等.马蹄香精油的化学成分研究.[J].云南植物研究,1980,2(1):59-60
[8]明东升,等.四种缬草生药挥发油化学成分的气相层析:质谱联用鉴定.中成药,1994,16(1):41-42
[9]Ming,Dong sheng;Yu,De Quan et al.The structures of three novel sesquiterpenoids from Valeriana jatamansi Jones.Tetrahedron Letters,1997,38(29),5205-5208
[10]Marayanan CS,etal.Terpenoids-XLⅥ..Components of India valerian port oil.Tetrahedron.1964,20(4):963
[11]Kulkarin KS,etal.Terpenoids-XLⅧ.Structures and stereo chemistry of hydroxyl valeranone and acetylhy drevaleranone.Tetrahedron,1964,20(5):1289
[12]王海来,等.蜘蛛香超临界CO_2萃取物化学成分的研究。北京中医药大学学报,2007,30(12):832-835
[13]ThiesPW.TetrahedronLett.1966,11:1163
[14]Thies PW.Die Konstitution der valepetriate mitteilung(?) die wirkstoffe des Baldrians.Tetrahedron,1968,24(1):313
[15]Thies PW.Active component ofvaleriana species.Tetrahedron Lett.1970,28:2471
[16]张人伟,等.云南植物研究.1986,8(1):107.
[17]明东升等.缬草类生药中总缬草素的含量测定,上海医科大学学报,1993,20(3):210
[18]崔亚君等.七种缬草属植物中的缬草素和乙酰缬草素含量考察.西北药学杂志,1999,14(4):152
[19]陈磊.三种缬草属植物的缬草素类含量种间和种内比较.中药材.2002,25(4):237
[20]肖丹,等.蜘蛛香药材中总缬草素的含量测定.时珍国医国药.2006,17(2):198-199
[21]VoderHudeW.Mutat Res.1986,169(1/2):23
[22]Fursa NS,etal.Study of the flavoncid composition of common valerian of the Asian part of the USSR.Farm Zh.1980,3:72
[23]石晋丽,等.HPLC法测定不同产地蜘蛛香中橙皮苷的含量.[J].中草药,2005,36(3):449-450
[24]曹斌,等.蜘蛛香中枢抑制作用.[J].中国中药杂志,1994,19(1):41-42
[25]陈磊,等.总缬草素类的质量标准和镇静催眠活性研究.中成药.2003,25(8):663-665
[26]Hazeheff B,etal.Antispasmodic effect of valeriana compounds:an in-vivo and in-vitro study on the guinea-pig ileum.Arch Int Pharmacodyn Ther.1982,257(2):274-287
[27]唐久余,等.缬草对慢性应激导致的抑郁大鼠大脑海马5-羟色胺水平、细胞增殖及神经元的影响.中西医结合学报.2008,6(3):283-288
[28]闫智勇,等.蜘蛛香对焦虑型大鼠行为学及脑组织神经递质含量的影响.中药药理与临床.2008,24(3):67-69
[29]梅秀英.中西医治疗护理一例滞泄腹痛体会.护理进修杂志.1990,5(1):48
[30]云南省小儿腹泻防治协作组.马蹄香治疗轮状病毒肠炎研究.中华儿科杂志.1985,23(3):129-131
[31]马静,等.马蹄香治疗小儿病毒性腹泻机理研究.云南中医杂志.1987,8(4):1-3
[32]魏群德,等.马蹄香治疗非轮状病毒肠炎的疗效观察.实用医学杂志.1992,4:3-4
[33]腾初兴,等.秋泻灵的毒性及其对肠肌功能的观察.昆明医学院学报.1986,7(2):23-25
[34]吴华欣.缬草属植物化学成分及药理作用研究的回顾.云南中医杂志.1985,1:9-51
[35]C Bounthanh,etal.Valepotriates,a new class of Cytotoxic and Antitumar Agents.PlantaMed.1981,41::21-28
[36]邓君,等.缬草的研究进展.国外医药植物药分册.2000,15(2):53-56
1 蜘蛛香环烯醚萜对正常小鼠的胃肠运动有一定的抑制作用。
2 蜘蛛香环烯醚萜可缓解利血平化小鼠的胃肠功能亢进。
3 蜘蛛香环烯醚萜可降低慢性应激所致IBS模型大鼠的内脏敏感性。
4 蜘蛛香环烯醚萜可显著减少IBS模型大鼠的排便量。
[1]薛征,关建红.脾肾两助丸抗抑郁的实验研究.中西医结合心脑血管病杂志,2003,1(12):714-715
[2]施新猷.医学实验动物学.北京:人民军医出版社,1999:380-383
[3]郭玉婷,李延青,庄明蕊,等.替加色罗治疗内脏高敏感大鼠前后感觉阈值的变化.胃肠病学和肝病学杂志,2004,13(4):337-380
[4]Emeran A,Brace D,Lin Chang,et al.Stress and irritable bowel syndrome.Am J Physiol Gastrointest Liver Physiol,2001,280:G519-G524
[5]Williams CL,Villar RG,Peterson JM,et al.Stress-induced changes in intestinal transit in the rats - A model for irritable bowel syndrome.Gastroenterology,1988,94;611-621
[6]Ness TJ,Gebhart GF.Colorectal distension as a noxious visceral stimulus:physiologic and pharm acologic characterization of pseudaffective refoexes in the rat.Brain Res,1988,45:153-169
[1]Benelli A,Filaferro M,Bertolini A,et al.Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats.Btitish Journal of pharmacology,1999(127):645-654
[2]郁镠宇.抑郁障碍生化与慢性应激动物模型的建立及行为学评价.广西医科大学学报,2008,25(4):596-598
[3]Willner P,Mitchell PJ.The validity of animal models of predisposition to depression.Behavioural Pharmocology,2002,13:169-188
3 蜘蛛香环烯醚萜不参与调节慢性应激所致IBS大鼠模型色氨酸羟化酶的转录表达。
4 蜘蛛香环烯醚萜对慢性应激所致IBS大鼠模型结肠和血浆中的SP有降低作用和对血中VIP降低,而结肠中VIP升高趋势,可降低结肠中SP/VIP值。
5 蜘蛛香环烯醚萜对慢性应激所致IBS大鼠模型结肠肥大细胞可能有降低作用。
[1]陈文科,邹益友,李富军,等.肠易激综合征精神心理因素、肠粘膜肥大细胞及5-羟色胺的变化.世界华人消化杂志,2007,15(1):46-50
[2]姜敏,凌立平,傅宝玉.5-羟色胺在肠易激综合征中作用的研究.中国医科大学学报,2006,35(2):171-172
[3]Mertz H,Morgan V,Tanner G,et al.Regional cerebral activitation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention.Gastroenterology,2000,118(5):842-848
[4]张彬彬,焦杨文,蔡卫民,等.Smads在日本血吸虫病小鼠肝纤维化形成过程中的表达.中国寄生虫学与寄生虫病杂志,2004,22(3):93-96
[5]张鑫,常笑雪,杨石强,等.血管活性肠肽及其类似物对大鼠腹腔肥大细胞功能的影响.河南科技大学学报,2008,26(3):161-164
[6]杨银芳,楚更五,张建英,等.痛泻要方对寒冷-束缚肠易激综合征模型大鼠作用的实验研究.中华中医药学刊,2008,26(9):1984-1986
[7]陈晓敏,张燕华,毛峻岭,等.肠易激综合征患者结肠粘膜P物质、血管活性肠肽和肥大细胞的变化.胃肠病学,2008,13(4):228-230
[8]O'Sullivan M,Clayton N,Breslin NP,et al.Increased mast cells in the irritable bowel syndrome.Neurogaastroenterol Motil.2000,12:449-457
[2]刘方,王承党.肠道感染和肠道菌群鱼肠易激综合征.国际消化病杂志,2008,28(1):23-25
[3]Vergrnolle N,Renaux B,Hollenberg MD,et al.Role of rat mast cell protease-2 in intestinal transport and barrier function.Gast roenterology,1998,114(suppl):A674
[4]Van der Waaji D.History of recognition and measurement of colonization resistance of the digestive tract as an introduction to selective gastrointestinal decontamination.Epidemiol Infec,1992,109:315-326
[5]刘俊康,闫国华,章荣华,等.细菌潜生体与IBS关系的初步研究.第三军医大学学报,2007,29(4):321-323
[6]Cruz Ruiz MA,Ortiz Herrera RB.Muniz Jurado D.et al.Association of depression and anxiety in patients with irritable bowel syndrome(Article in Spanish).Rev Gastroenterol Mex,2007,72(1):29-33.
[7]高保华,刘长宁.肠易激综合征的心理社会因素研究.中国社区医师,2007,9(6):25
[8]陈钟鸣,高小燕,黄六英,等.肠易激综合征患者焦虑抑郁评价报告.实用临床医学,2008,9950;44-46
[9]Locke GR,Zinsmeister AR,Talley N J et al.Familial association in adults with functional gastrointestinal disorders[J].Mayo Clin Proc,2000,75(9):907-912
[10]Levy RL,Jones KR,Whitehead WE,et al.Irritable bowel syndrome in twins heredity and social learning both contribute to etiology[J].Gastroentero,2001,121(4):799-804
[11]Houghton LA,Jackson NA,Whorwhell P J,et al.Do male sex hormones protect from irritable bowel syndrome?[J].Am J Gastroentero J.2000,95(9):2296-2300
[12]孔庆建,张辉,孙波,等.肠易激综合征的病因与发病机制.中国煤炭工业医学杂志.2006,9(10):1033-1034
[13]游元明,刘劲松.肠易激综合征感觉异常研究进展.国际消化病杂 志.2007,27(3):167-169
[14]詹丽杏,许国铭,李兆申,等.肠易激综合征患者活动期和缓解期血浆5-羟色胺、5-羟吲哚乙酸的变化.第二军医大学学报,2003,24(2):152-154
[15]Delgado M,Pozo D,Ganea D.The Significance of vasoactive intestinal peptide in immunomodulation.Pharmacol Rev,2004,56(2):249-290
[16]陈晓敏,张燕华,毛峻岭,等.肠易激综合征患者结肠粘膜P物质、血管活性肠肽和肥大细胞的变化.胃肠病学,2008,13(4):228-230
[17]宋继中,王巧民,丁西平,等.肠易激综合征患者结肠粘膜神经肽和IL-1β变化及其意义.胃肠病学和肝病学杂志.2007,16(3):219-222
[18]梁荣新,郑琴芳,梁列新,等.肠易激综合征与胃肠激素的关系.中国综合临床,2004,20(8):702-703
[19]王伟岸,钱家鸣,潘国宗.结肠粘膜肥大细胞活化在肠易激综合征发病中的作用.中华消化杂志.2003,23(5):263-266
[20]董文珠,邹多武,李兆申,等.肠易激综合征患者内脏高敏感性的机制研究.中华消化杂志,2004,24(1):18-22
[21]郭敏,李延青,刘传勇,等.肠易激综合征大鼠模型外周血免疫调节性T细胞的研究.山东大学学报(医学版).2006,44(5):514-518
[22]张海燕,吴萍,李延青,等.肠易激综合征患者的免疫学机制探讨.胃肠病学和肝病学杂志.2006,15(3):285-287
[23]Charles DRM,Joanna F,Laura R,et al.Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome.Gastroenterology.2004,127(6):1695-1703
[1]周福生,廖荣鑫.肠易激综合征中西医诊断与治疗.北京:中国医药科技出版社.2007:40
[2]时乐,卜平,郑新梅,等.211例肠易激综合征证候病机的研究.中医研 究,2005,18(11):24-26
[3]梅武轩.肠易激综合征的中医辨治经验.辽宁中医学院学报,2005,7(5):444-445.
[4]钟海平.通肠舒痛饮治疗便秘型肠易激综合征97例.实用中医药杂志,2006,22(5):276-277
[5]崔莉红.从脾论治腹泻型肠易激综合征.陕西中医,2008,29(1):46-47
[6]章力勤.健脾化湿汤治疗肠易激综合征30例临床观察.浙江中医药大学学报,2006,30(3):245-246
[7]王金雁.痛泻要方合参苓白术散加减治疗腹泻型肠易激综合征50例.山西中医,2008,24(6):13-14
[8]陶云,董明霞,寇焰,等.疏肝健脾法治疗腹泻型肠易激综合征体会.北京中医,2006,25(8):458-460
[9]刘力,沈舒文.肠易激综合征中医辨证论治.实用中医内科杂志,2002,16(3):157-158
[10]苏佩仪.疏肝补脾健胃法治疗肠易激综合征96例疗效观察.河北中医,2004,26(5):345
[11]周福生,吴文江,张庆宏.胃肠功能性疾病证型分布的统计分析.中华国际医学杂志,2002,2(5):438,442
[12]吴成胜,苏良.从肝脾论治腹泻型肠易激综合征探微.山东中医药大学学报,2004,28(1):25-26
[13]李炜.辨证治疗肠易激综合征39例.山西中医,2004,20(5):17-18
[14]王庆成.辨证治疗肠易激综合征56例.河南中医,2004,24(4):32-33
[15]赵爱莲.辨证分型治疗肠易激综合征172例.江西中医药,2006,5:28-29
[16]范汉淮.辨证分型治疗腹泻型肠易激综合征40例.辽宁中医学院学报,2006,8(1):47-48
[17]孙长清,李联社.理气健脾汤治疗肠易激综合征160例.陕西中医,2008,29(2):189-190
[18]许慧玲,尹俊芳,叶松.自拟固肠汤治疗腹泻型肠易激综合征45例临床观察.山西中医学院学报,2008,9(2):33-34
[19]王金雁.痛泻要方合参苓白术散加减治疗腹泻型肠易激综合征50例.山西中医,2008,24(6):13-14
[20]张蜀,吴至久,廖伯年.逍遥散加味治疗便秘型肠易激综合征27例.实用中医内科杂志.2008,22(3):31
[21]王长来.养血通腑汤治疗便秘型肠易激综合征50例.江西中医药,2008,39(303):21
[22]高强,李慧臻.宣肺理气活血法治疗便秘型肠易激综合征38例.吉林中医药,2007,27(12):25-26
[23]武雪宇.辨证施针治疗肠易激综合征31例.上海针灸杂志,2006,25(6):25-26
[24]杨国梁,胡淑宏.中药合艾灸治疗肠易激综合征40例临床观察.针灸临床杂志,2004,20(7):13
[25]陈国源,梁萌,许树根,等.肠易激综合征中药配合穴位注射与心理治疗82例.中国中西医结合消化杂志,2006,14(2):124-125
[26]谢胜,张志杰,梁谊深.中草药蒸汽疗法合指针治疗肠易激综合征64例.陕西中医,2006,27(1):54-55
[27]陈春永,郑永臻,朱迪盈.健脾补肾中药联合培菲康治疗腹泻型肠易激综合征44例.世界中医药,2008,3(3):163
[28]董晓明.中西医结合治疗腹泻型肠易激综合征60例.中国中西医结合消化杂志,2006,14(6):410-411
[29]华军.中西医结合治疗肠易激综合征40例.中国中西医结合消化杂志,2006,14(1):53-54
[30]蓝惠玲,刘友章,李耿成,等.加味痛泻要方颗粒治疗腹泻型肠易激综合征42例疗效观察.新中医,2005,37(5):26-27
[31]彭慕斌,田英.复方黄连素片治疗肝郁脾虚型肠易激综合征48例.职业与健康,2005,21(12):2040-2041
[32]谢建群,潘相学.健脾温中法对脾胃虚寒型肠易激综合征模型大鼠生长抑素的影响.中医杂志,2004,45(9):697-699
[33]谢建群,郑昱,吴大正,等.疏肝饮对腹泻型肠易激综合征大鼠血管活性肠肽和P物质的影响.上海中医药大学学报,2004,18(3):36-39
[34]王海云,石君杰.宁肠汤治疗大鼠肠易激综合征的实验研究.中国中医药科技,2003,10(5):266-269
[35]王海云,石君杰,李新伟.宁肠汤对肠易激综合征大鼠下丘脑-垂体-肾上腺轴干预作用的研究.中国中医药科技,2006,13(6):393-394
[36]石君杰.宁肠汤对肠易激综合征大鼠炎性细胞因子影响的实验研究.中国中医药科技,2008,15(2):103-104
[37]周福生,吴文江,黄志新.顺激合剂对肠易激综合征患者结肠动力学影响的研究.中医杂志,2004,45(11):856-858
[38]沈骏,诸琦,袁耀宗,等.肠吉安口服液对肝脾不和腹泻型肠易激综合征患者大脑功能区激活面积的影响.中国中西医结合消化杂志,2005,13(4):218-222
[39]霍清萍,张仲伟,王兵,等.调肝运脾方对腹泻型肠易激综合征患者脑内兴奋区域活动的影响.上海中医药杂志,2007,41(11):40-43
[40]占宏伟,项康柏,陈芝芸,等.肠易激综合征不同中医证型前列腺素E_2和环核苷酸的变化及意义.浙江中医学院学报,2000,24(3):16-18
[41]陈芝芸,严茂祥,项柏康.肠易激综合征中医证型与胃肠激素关系的探讨.中国中西医结合杂志,2002,22(9):664-666
[1]Coutinho S,Plotsky PM,Sablad M,et al.Neonatal maternal separation alters stress-induced response to viscerosomatic nociceptive stimuli in rats.Am J Physiol Gastrointest Liver Physio,2002,282:307-316
[2]Williams CL,Villar RG,Peterson JM,et al.Stress-induced changes in intestinal transit in the rats-A model for irritable bowel syndrome.Gastroenterology,1988,94;611-621
[3]李延青,杨云生,陈建.肠易激综合征.北京:中国医药科技出版社.2005:94
[4]Tache Y,Garrick T,Raybouid H.Central nervous system action of peptides to infulence gastrointestinal motor function.Gastroenterology,1990,98(2):517-518
[5]collions SM,McHugh K,Jacobson K,et al.Previous inflammation alters the response of the rat colon to stress.Gastroenterology.1996 Dec,111(6):1509-1515
[6]Al-Chaer ED,Kawasaki M,Pasricha PJ.A new model of chronic visceral hypersensitivity in adult rats incluced by colon irritation during postnatal development.Gastroenterology,2000,119(5):1276-1285
[7]Scott RB,Tan DT,Miampamba M,et al.Anaphy-laxis-induced alterations in intestinal motility:role of extrimsic neural pathways.Am-J-Physiol,1998,275(4 Pt 1):G812-821
[8]胡萍萍,吕宾,范一宏.内脏高敏感大鼠脑部5-羟色胺表达差异的研究.中华消化杂志,2006,26(5):347-348
[9]Ness TJ,Gebhart GF.Colorectal distension as a noxious visceral stimulus:physiologic and phar,,,logic characterization of pseudaffective refle,,,in the rat.Brain Res,1988(4),450:153-169
[1O]Chen JJ,Li Z,Pan H,etal.Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter abnormal intestinal motility and the expression of cation transporters.J Neurosci,2001,21:6348-6361
[11]彭丽华,杨云生,孙刚,等.便秘型肠易激综合征新概念模型的建立.世界华人消化杂志,2004,12(1):112-116
[12]徐俊荣,罗金燕.肠易激综合征动物模型研究进展.基础医学与临床.2006,26(8):902-904
[13]Naliboff BD,Chang L,Munakata J,et al.Towards an integrative model of irritable bowel syndrome.Prog Brain Res,2000,122:413-423
[1]Chen JX,Pan H,Rothman TP,et al.Guinea pig 5-HT transporter:Cloning,expression,distribution and function in intestinal sensory reception.Am J Physiol,1998;275:G433-G448
[2]Gershon MD,Tack J(2007) The serotonin signaling system:from basic understanding to drug development for functional GI disorders.Gastroenterol,2007,132:397-414
[3]詹丽杏,许国铭,李兆申,等.肠易激综合征患者活动期和缓解期血浆5-HT、5-HIAA的变化.第二军医大学学报,2003,24(2):152-154
[4]Gershon MD.Review article:serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motility.Aliment Pharmacol Ther 20(Suppl7):3-14
[5]Pan H,Gershon MD.Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine.J Neurosci 20:3295-3309
[6]Grider JR.Neurotransmitters mediating the intestinal peristaltic reflex in the mouse.J Pharmacol Exp Ther 307:460-467
[7]迟燕,刘新光,李江.5-羟色胺4受体在调解应激大鼠内脏敏感性中的作用.中华消化杂志,2003,24(9):533-536
[8]丁斐,神经生物学.北京:科学出版社.2007:174-175
[9]孙凤艳.医学神经生物学.上海:上海科学技术出版社.2008:148
[10]陈钟鸣,高小燕,黄六英,等.肠易激综合征患者焦虑抑郁评价报告.实用临床医学,2008,9950;44-46
[11]Ringel Y,Drossman DA,Turkington TG,et al.Dysfunctions of the motivational affective pain system inpatients with IBS:PET brain imaging in response to rectal ballon distention.Gastroenterology,2000(suppl):A474
[12]胡萍萍,吕宾,范一宏.内脏高敏感大鼠脑部5-羟色胺表达差异的研究.中华消化杂志,2006,26(5):347-348
[13]孙刚,杨云生,彭丽华,等.肠易激综合征大鼠内脏敏感性异常与结肠及中枢神经系统5-HT和c-fos表达的关系.胃肠病学和肝病学杂志.2008,17(4):313-317
[14]Hartig PR,Hoyer D,Humphrey PP,et al.Alignment of receptor nomenclature with the human genome classification of 5-HT1B and 5-HT1D receptor subtypes.Trends Pharmacol Sci,1996,17:1003-1005
[15]Hoyer,D,Hannon JP,Martin GR.Molecular,pharmacological and functional diversity of 5-HT receptors.Pharmacol Biochem Behav,2002,71:533-554
[16]Sanger GJ,Andrews PLR.Treatment of nausea and vomiting:gaps in our knowledge.Autonom Neurosci Basic Clin,2006,129:3-16
[17]Davies PA,Pistis M,Hanna MC,et al.The 5-HT3B subunit is a major determinant of serotonin-receptor function.Nature,1999,397:359-363
[18]Niesler B,Frank B,Kapeller J,et al.Cloning,physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C,HTR3D and HTR3E.Gene,2003,310:101-111
[19]Glatzle J,Stemini C,Robin C,et al.Expression of 5-HT3 receptors in the rat gastrointestinal tract.Gastroenterology,2002,123:217-226
[20]Raybould HE,Glatzle J,Robin C,et al.Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying.Am J Physiol,2003,284:G367-G372
[21]王静,5-羟色胺受体及转运体在肠易激综合征发病机制中的作用.上海交通大学学报(医学版),2008,26(8):1051-1054
[22]Bender E,Pindon A,Van Oers I,et al.Structure of the human serotonin 5-HT4receptor gene and cloning of a novel 5-HT4 splice variant.J Neurochem,2000,74:478-489
[23]Galligan JJ,LePard KJ,Schneider DA,et al.Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system.J Auton Nerv Syst,2000,81:97-103
[24]Wouters MM,Farrugia G,Schemann M.5-HT receptors on interstitial cells of Cajal,smooth muscle and enteric nerves.Neurogastroenterol Motil 2007,19(Suppl 2):5-12
[25]Clayton NM,Sargent R,Butler A,et al.The pharmacological properties of the novel selective 5-HT3 receptor antagonist,alosetron,and its effects on normal and perturbed small intestinal transit in the fasted rat.Neurogastroenterol Motil,1999
[26]Mori T,Kawano K,Shishikura T.5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats.J Pharmacol Sci,2004,94:73-7
[27]Gershon MD,Tack J.The serotonin signaling system:from basic understanding to drug development for functional GI disorders.Gastroenterol,2007,132:397-414
[28]Berman SM,Chang L,Suyenobu B,et al.Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist alosetron.Gastroenterology,2002,123:969-977
[29]Bradesi S,Lao L,McLean PG,et al.Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia.Pain,2007,130:56-65
[30]Kaumann AJ,Levy FO.5-hydroxytryptamine receptors in the human cardiovascular system.Pharmacol Ther,2006,111:674-706
[31]林懋惺,杨丽.5-羟色胺受体与肠易激综合征.医学综述,2007,13(5):398-400
[32]Baker DE.Rationale for USing serotonergic agents to treat irritable bowel syndrome.Am J Health-Syst Pharm,2005,62:700-711
[33]Gershon MD.Nerves,reflexes,and the enteric nervous system.J Clin Gastroentero1,2005,39:S184-S193
[34]Galligan JJ,Pan H,Messori E.Signalling mechanism Coupled to 5-hydfoxytryptamine4 receptor-mediated facilitation of fast synaptic transmission in the guinea pig ileum myenteric plexus.Neurogastroenterol Motil,2003,15:523-529
[35]Taniyama K,Makimoto N,Furuichi A,et a1.Functions of peripheral 5-hydfoxytryptamine receptors,especially 5-hydroxytryptamine4 receptor,in gastrointestinal motility.J Gastroenterol,2000,35:575-582
[36]Cellek S,John AK,Thangiah R,et al.5-HT4 receptor agonists enhance both cholineric and nitrergic actiVities in human isolated colon circular muscle.Neurogastroenterol Motil,2006,18:853-861
[37]Tam FS,Hillier K,Bunce KT.Characterization of the 5-hydfoxytryptamine receptOr type involved in inhibition of spontaneous actiVity Of human isolated colonic circular muscle.Br J Pharmacol,1994,113:143-150
[38](?) B,(?) M,(?) G.Serotonin increases protective duodenal bicarbonate secretion Via ellteric ganglia and a 5-HT4-dependent pathway.Scand J Gastroenterol,2006,41:1279-1289
[39]BoriBan RA,Burleigh DE.Heterogerieity of 5-HT receptors mediating secretion in the human intestine.Ann NY Acad Sci,1997,812:224-225
[40]Greenwood-Van Meerveld B,Venkova K,et al.ActiVation of peripheral 5-HT receptors attenuates colonic sensitiVity to intraluminal distension.Neurogastroenterol Motil,2006,18:76-86
[41]Sun YN,Luo JY.Effects of tegaserod on Fos,substance P and calcitonin gene-related peptide expressiOn induced by colon innammation in 1umbarsacral spinal cord.World J Gastroenterol,2004,10:1830-1833
[42]Degen L,Petrig C,Studer D,et al.Effect of tegaserod on gut transit in male and female subjects.Neurogastroenterol Motil,2005,17:821-826
[43]王静,5-羟色胺受体及转运体在肠易激综合征发病机制中的作用.上海交通大学学报(医学版),2008,26(8):1051-1054
[44]Camilleri M,Andrews CN,Bharucha AE,et al.Alterations in expression of pll and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome.Gastroenterology,2007,132:17-25
[45]Van Lelyveld N,Ter Linde J,Schipper ME,et al.Regional differences in expression of TPH-1,SERT,5-HT(3) and 5-HT(4) receptors in the human stomach and duodenum.Neurogastroenterol Motil,2007,19:342-34
[46]Coates MD,Mahoney CR,Linden DR,et al.Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology,2004,126:1657-1664
[47]代子艳,王巧民.5-羟色胺转运体基因多态性与肠易激综合征.国际消化杂志,2008,28(5):364-367
[48]Spigset O.Adverse reactions of selective reuptake inhibitors:reports from a spontaneous reporting system.Drug Saf,1999,20:277-287
[49]Coates MD,Johnson AC,Greenwood-Van Meerveld B,et al.Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse.Neurogastroenterol Motil,20016,18:464-471
[50]Chen JJ,Zhishan L,Pan H,et al.Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter(SERT):abnormal intestinal motility and the expression of cation transporters.J Neurosci,2001,21:6348-6361
[51]Talley NJ.Pharmacologic therapy for the irritable bowel syndrome.Am J Gastroenterol,2003,98:750-758
[52]Tack J,Broekaert D,CorsettiM,et al.Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man.Aliment Pharmacol Ther,2006,23:265-274
[53]Kuiken SD,Tytgat GN,Boeckxstaens GE.The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome:a double blind,randomized,placebo-controlled study.Clin Gastroenterol Hepatol,2003,1:219-228
[1]兰茂著.《滇南本草》整理组整理,滇南本草,第二卷,昆明.云南人民出版社.1977.273
[2]李时珍.本草纲目,第二册.北京:人民卫生出版社,1979:845
[3]中华人民共和国卫生部药典委员会编.中华人民共和国药典,1977年版,一部.北京:人民卫生出版社,1978:633
[4]吴家荣.中草药蜘蛛香(印度缬草)的鉴定研究.新医药通讯,1976,1:73-78
[5]郭济贤,等.缬草类专题研究.《常用中药材品种整理和质量研究》第二册,福建科学技术出版社,1997:490
[6]刘娟,等.缬草属药用植物的研究进展.黑龙江医药科学,2007,(30)1:94-95
[7]王宗玉,等.马蹄香精油的化学成分研究.[J].云南植物研究,1980,2(1):59-60
[8]明东升,等.四种缬草生药挥发油化学成分的气相层析:质谱联用鉴定.中成药,1994,16(1):41-42
[9]Ming,Dong sheng;Yu,De Quan et al.The structures of three novel sesquiterpenoids from Valeriana jatamansi Jones.Tetrahedron Letters,1997,38(29),5205-5208
[10]Marayanan CS,etal.Terpenoids-XLⅥ..Components of India valerian port oil.Tetrahedron.1964,20(4):963
[11]Kulkarin KS,etal.Terpenoids-XLⅧ.Structures and stereo chemistry of hydroxyl valeranone and acetylhy drevaleranone.Tetrahedron,1964,20(5):1289
[12]王海来,等.蜘蛛香超临界CO_2萃取物化学成分的研究。北京中医药大学学报,2007,30(12):832-835
[13]ThiesPW.TetrahedronLett.1966,11:1163
[14]Thies PW.Die Konstitution der valepetriate mitteilung(?) die wirkstoffe des Baldrians.Tetrahedron,1968,24(1):313
[15]Thies PW.Active component ofvaleriana species.Tetrahedron Lett.1970,28:2471
[16]张人伟,等.云南植物研究.1986,8(1):107.
[17]明东升等.缬草类生药中总缬草素的含量测定,上海医科大学学报,1993,20(3):210
[18]崔亚君等.七种缬草属植物中的缬草素和乙酰缬草素含量考察.西北药学杂志,1999,14(4):152
[19]陈磊.三种缬草属植物的缬草素类含量种间和种内比较.中药材.2002,25(4):237
[20]肖丹,等.蜘蛛香药材中总缬草素的含量测定.时珍国医国药.2006,17(2):198-199
[21]VoderHudeW.Mutat Res.1986,169(1/2):23
[22]Fursa NS,etal.Study of the flavoncid composition of common valerian of the Asian part of the USSR.Farm Zh.1980,3:72
[23]石晋丽,等.HPLC法测定不同产地蜘蛛香中橙皮苷的含量.[J].中草药,2005,36(3):449-450
[24]曹斌,等.蜘蛛香中枢抑制作用.[J].中国中药杂志,1994,19(1):41-42
[25]陈磊,等.总缬草素类的质量标准和镇静催眠活性研究.中成药.2003,25(8):663-665
[26]Hazeheff B,etal.Antispasmodic effect of valeriana compounds:an in-vivo and in-vitro study on the guinea-pig ileum.Arch Int Pharmacodyn Ther.1982,257(2):274-287
[27]唐久余,等.缬草对慢性应激导致的抑郁大鼠大脑海马5-羟色胺水平、细胞增殖及神经元的影响.中西医结合学报.2008,6(3):283-288
[28]闫智勇,等.蜘蛛香对焦虑型大鼠行为学及脑组织神经递质含量的影响.中药药理与临床.2008,24(3):67-69
[29]梅秀英.中西医治疗护理一例滞泄腹痛体会.护理进修杂志.1990,5(1):48
[30]云南省小儿腹泻防治协作组.马蹄香治疗轮状病毒肠炎研究.中华儿科杂志.1985,23(3):129-131
[31]马静,等.马蹄香治疗小儿病毒性腹泻机理研究.云南中医杂志.1987,8(4):1-3
[32]魏群德,等.马蹄香治疗非轮状病毒肠炎的疗效观察.实用医学杂志.1992,4:3-4
[33]腾初兴,等.秋泻灵的毒性及其对肠肌功能的观察.昆明医学院学报.1986,7(2):23-25
[34]吴华欣.缬草属植物化学成分及药理作用研究的回顾.云南中医杂志.1985,1:9-51
[35]C Bounthanh,etal.Valepotriates,a new class of Cytotoxic and Antitumar Agents.PlantaMed.1981,41::21-28
[36]邓君,等.缬草的研究进展.国外医药植物药分册.2000,15(2):53-56
1 蜘蛛香环烯醚萜对正常小鼠的胃肠运动有一定的抑制作用。
2 蜘蛛香环烯醚萜可缓解利血平化小鼠的胃肠功能亢进。
3 蜘蛛香环烯醚萜可降低慢性应激所致IBS模型大鼠的内脏敏感性。
4 蜘蛛香环烯醚萜可显著减少IBS模型大鼠的排便量。
[1]薛征,关建红.脾肾两助丸抗抑郁的实验研究.中西医结合心脑血管病杂志,2003,1(12):714-715
[2]施新猷.医学实验动物学.北京:人民军医出版社,1999:380-383
[3]郭玉婷,李延青,庄明蕊,等.替加色罗治疗内脏高敏感大鼠前后感觉阈值的变化.胃肠病学和肝病学杂志,2004,13(4):337-380
[4]Emeran A,Brace D,Lin Chang,et al.Stress and irritable bowel syndrome.Am J Physiol Gastrointest Liver Physiol,2001,280:G519-G524
[5]Williams CL,Villar RG,Peterson JM,et al.Stress-induced changes in intestinal transit in the rats - A model for irritable bowel syndrome.Gastroenterology,1988,94;611-621
[6]Ness TJ,Gebhart GF.Colorectal distension as a noxious visceral stimulus:physiologic and pharm acologic characterization of pseudaffective refoexes in the rat.Brain Res,1988,45:153-169
[1]Benelli A,Filaferro M,Bertolini A,et al.Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats.Btitish Journal of pharmacology,1999(127):645-654
[2]郁镠宇.抑郁障碍生化与慢性应激动物模型的建立及行为学评价.广西医科大学学报,2008,25(4):596-598
[3]Willner P,Mitchell PJ.The validity of animal models of predisposition to depression.Behavioural Pharmocology,2002,13:169-188
3 蜘蛛香环烯醚萜不参与调节慢性应激所致IBS大鼠模型色氨酸羟化酶的转录表达。
4 蜘蛛香环烯醚萜对慢性应激所致IBS大鼠模型结肠和血浆中的SP有降低作用和对血中VIP降低,而结肠中VIP升高趋势,可降低结肠中SP/VIP值。
5 蜘蛛香环烯醚萜对慢性应激所致IBS大鼠模型结肠肥大细胞可能有降低作用。
[1]陈文科,邹益友,李富军,等.肠易激综合征精神心理因素、肠粘膜肥大细胞及5-羟色胺的变化.世界华人消化杂志,2007,15(1):46-50
[2]姜敏,凌立平,傅宝玉.5-羟色胺在肠易激综合征中作用的研究.中国医科大学学报,2006,35(2):171-172
[3]Mertz H,Morgan V,Tanner G,et al.Regional cerebral activitation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention.Gastroenterology,2000,118(5):842-848
[4]张彬彬,焦杨文,蔡卫民,等.Smads在日本血吸虫病小鼠肝纤维化形成过程中的表达.中国寄生虫学与寄生虫病杂志,2004,22(3):93-96
[5]张鑫,常笑雪,杨石强,等.血管活性肠肽及其类似物对大鼠腹腔肥大细胞功能的影响.河南科技大学学报,2008,26(3):161-164
[6]杨银芳,楚更五,张建英,等.痛泻要方对寒冷-束缚肠易激综合征模型大鼠作用的实验研究.中华中医药学刊,2008,26(9):1984-1986
[7]陈晓敏,张燕华,毛峻岭,等.肠易激综合征患者结肠粘膜P物质、血管活性肠肽和肥大细胞的变化.胃肠病学,2008,13(4):228-230
[8]O'Sullivan M,Clayton N,Breslin NP,et al.Increased mast cells in the irritable bowel syndrome.Neurogaastroenterol Motil.2000,12:449-457