摘要
目的:肠易激综合征(irritable bowel syndrome, IBS)是一种因肠道高敏感性所致的肠道应激性疾病,是指一组包括腹痛、腹胀、腹泻,病因和发病机制迄今尚未阐明的功能性肠紊乱症候群。随着生活节奏的不断加快和社会竞争的日趋激烈,国内外发病率在不断上升,严重影响了人们正常的工作、学习和生活。
IBS的病因和发病机制迄今尚未阐明。目前认为内脏敏感性增高是IBS最重要的病理生理特征之一,是IBS病人症状产生的基础和症状多样化的原因。近年来研究提示,肥大细胞在肠道应激性疾病发生的病理生理过程中起关键作用,肥大细胞被活化后,可释放许多生物活性不同的介质,介质释放可进一步放大各种生理病理反应,从而导致各种症状的发生。所以,通过抑制肠道肥大细胞活化,使其减少释放组胺、P物质等介质的数量,是治疗肠道应激性疾病的关键所在。
IBS发病机制复杂,涉及精神、饮食、个体素质多个方面,单一药物临床作用局限,不能满足临床要求。祖国传统医学亦认为,腹痛泄泻成因复杂,治法也多。健脾解毒化浊方是著名中医专家李佃贵教授经多年临床实践总结出来的经方,由白头翁、黄连、黄芩、人参、黄芪、白术、白芍、陈皮、防风、秦皮、苦参、地榆、木香、薏米、当归、甘草等组成,具有解毒化浊、舒肝健脾、清热燥湿之功效,健脾解毒化浊方经过长期的临床观察,对IBS有较好的疗效。为了进一步探讨健脾解毒化浊方治疗IBS的药理作用及其机理,本研究从药理学研究出发,以肥大细胞功能研究为重点,应用血液生化学、药物血清学、免疫组织化学、体外细胞培养,以及分子生物学方法,分别通过对内脏高敏感性IBS大鼠模型行为学和电生理指标、血生化的监测,对大鼠腹腔肥大细胞脱颗粒现象的观察,以及对大鼠腹腔肥大细胞表面抗体的研究,试图从器官水平、细胞水平和基因水平三个方面来探讨健脾解毒化浊方对IBS的疗效和作用机理,并结合健脾解毒化浊方在临床上的实际应用疗效研究,为发挥中药名方多途径、多靶点及整体治疗的优势,科学开发利用中药名方提供科学依据,同时为新药的开发打下基础。
方法
第一部分健脾解毒化浊方对内脏高敏性肠易激综合征大鼠模型的疗效和作用机理的实验研究
实验一:采用结肠醋酸慢性刺激法制作内脏高敏感性的IBS大鼠模型。造模分为幼年大鼠结肠醋酸慢性刺激组(NA组)、成年大鼠结肠醋酸慢性刺激组(AA组)和空白对照组(NS组)。造模后对各组IBS大鼠模型分别进行内脏敏感性评估(腹壁肌电活动和腹部回缩反射),以验证造模是否成功。
实验二:探讨健脾解毒化浊方对内脏高敏感性IBS大鼠模型的疗效和作用机理。造模成功后,将实验动物分为空白对照组(A组)、模型对照组(B组)、得舒特组(C组)、健脾解毒化浊方低剂量组(D组)、健脾解毒化浊方高剂量组(E组)。观察各组大鼠在不同因素影响下的肠道内扩张引起腹部抬起和背部拱起的容量阈值和大鼠肠道内不同容量下扩张期间腹壁收缩次数,检测5-羟色胺(5-HT)、P物质(SP)、降钙素基因相关肽(CGRP)含量。
第二部分健脾解毒化浊方药物血清对大鼠腹腔肥大细胞受抗原活化时脱颗粒的影响
制备大鼠腹腔肥大细胞悬液,并进行鉴定。同时制备健脾解毒化浊方药物血清、西药治疗组药物血清及对照组空白血清。实验分为健脾解毒化浊方药物血清高低两个剂量组为中药治疗组,色甘酸钠组为西药治疗组,加空白血清及C48/80的作为阳性对照组,只加空白血清的作为空白对照组。分别观察各组药物血清对大鼠腹腔肥大细胞活化脱颗粒释放组胺及TNF-α的影响;各组药物血清对大鼠腹腔肥大细胞活化脱颗粒时细胞形态的影响;应用钙离子荧光指示剂Fluo-3,通过电镜和激光共聚焦荧光显微镜,观察健脾解毒化浊方对大鼠腹腔肥大细胞受抗原活化时脱颗粒百分数及肥大细胞内游离钙浓度和组胺释放的影响。
第三部分健脾解毒化浊方含药血清抑制大鼠腹腔肥大细胞脱颗粒的分子生物学机制
制备大鼠腹腔肥大细胞悬液,并进行鉴定。同时制备健脾解毒化浊方药物血清及对照组空白血清。实验分为高剂量健脾解毒化浊方药物血清组、低剂量健脾解毒化浊方药物血清组和空白对照组。应用RT-PCR方法和免疫组织化学显色方法分别检测各组大鼠腹腔肥大细胞的TLR2和Fas的表达。
第四部分健脾解毒化浊方治疗腹泻型肠易激综合征的临床研究
采用前瞻性随机双盲、西药治疗平行对照研究方法。对参与的研究者进行诊断、纳入排除标准及实施方案的培训。从2004年12月至2006年12月共有137例腹泻型IBS患者进入研究,以1:1比例按随机数字进入中药治疗组和西药治疗组。中药治疗组口服健脾解毒化浊方,西药治疗组口服得舒特片。观察项目包括治疗前后的腹痛和大便情况,其它需观察的症状尚有排便急迫或胀坠感、胸胁或小腹胀闷、情绪紧张或抑郁恼怒时泻泄加重情况、黏液便、嗳气以及进食量等;体征检测包括结肠区压痛及舌脉象。治疗前及治疗3周停药后行血、尿常规,肝肾功能和心电图等检查。密切观察不良事件与不良反应,记录其发生的时间、表现、处理经过及结果,注意有无严重不良事件与不良反应发生。
结果
第一部分健脾解毒化浊方对内脏高敏性肠易激综合征大鼠模型的疗效和作用机理的实验研究
实验一:在造模第6周,NS组8只大鼠引起腹部抬高和背部拱起的扩张容量阈值分别为(0.70±0.10)ml和(0.94±0.16)ml,AA组大鼠上述两项阈值分别为(0.76±0.06)ml和(1.02±0.88)ml,二者差异无显著性(P>0.05)。而NA组大鼠腹部抬高和背部拱起阈值分别为(0.43±0.06)ml和(0.61±0.08)ml,与前两组相比差异有显著性(P值均<0.01);在0.5ml容量时,NS组和AA组大鼠的腹壁收缩并不明显,而NA组大鼠腹壁收缩数目达(6.63±1.06)次/5min,差异有显著性(P<0.01)。在0.8ml扩张容量下,NA组大鼠腹壁收缩活动均较另外两组更为显著(P<0.05)。在1.2ml扩张容量下,NA组大鼠较NS组大鼠腹壁收缩显著增强(P<0.05),而与AA组差异无显著性(P>0.05)。
实验二:在行为测试方面,用药后,B组与A组相比,引起大鼠腹部抬起和背部拱起的扩张容量阈值明显降低,差异显著(P<0.01,P<0.05),而C、D、E组与A组相比,均无显著差异(P>0.05);D、E组与C组相比,均无显著差异(P>0.05);腹壁肌电活动记录结果显示,用药后,B组与A组相比,在1.0ml、1.5ml扩张容量时,大鼠腹壁肌肉收缩次数明显增加,差异非常显著(P<0.01),而C、D、E组与A组相比,二者无显著差异(P>0.05),D、E组与C组相比,均无显著差异(P>0.05);与模型对照组相比,各治疗组大鼠行为学和电生理指标均有明显改善;各治疗组模型大鼠5-HT、SP含量明显下降,CGRP含量增加,且有一定的量效关系。
第二部分健脾解毒化浊方药物血清对大鼠腹腔肥大细胞受抗原活化时脱颗粒的影响
模型对照组大鼠腹腔肥大细胞脱颗粒百分数为65%,高剂量中药治疗组大鼠腹腔肥大细胞脱颗粒百分数为13%,低剂量中药治疗组大鼠腹腔肥大细胞脱颗粒百分数为23%,两组与模型对照组相比,差异均有显著性(p<0.05)。用光学显微镜观察,模型对照组的肥大细胞脱颗粒现象要明显多于高剂量中药治疗组,脱颗粒后的肥大细胞多呈空泡状。用激光共聚焦显微镜观察,直接用C48/80处理的模型对照组大鼠腹腔肥大细胞胞浆内充满绿色荧光,分布于细胞外侧,而高剂量中药组部分肥大细胞未见绿色荧光出现。加入高剂量中药药物血清的大鼠腹腔肥大细胞在C48/80处理后细胞状态以及胞浆钙染色的荧光强度则没有明显变化;模型对照组大鼠腹腔肥大细胞滤液组胺浓度为(98.41±7.23)nmol/L,高剂量中药组大鼠腹腔肥大细胞滤液组胺浓度为(33.23±21.50)nmol/L,两组差异有显著性(p<0.05)。
第三部分健脾解毒化浊方含药血清抑制大鼠腹腔肥大细胞脱颗粒的分子生物学机制
结果显示,大鼠腹腔肥大细胞用健脾解毒化浊方药物血清刺激后30min,TLR2mRNA/βactinmRNA比值及FasmRNA/βactinmRNA比值均增高,与空白对照组比较均有显著性差异(P均<0.05),证实健脾解毒化浊方药物血清可刺激TLR2mRNA和FasmRNA的表达,以健脾解毒化浊方高剂量组效果最明显,与对照组比较有显著性差异(P<0.05)。
免疫组化实验结果显示,兔抗小鼠mTLR2胞外段合成肽抗体TSP-2能与大鼠腹腔肥大细胞结合,而对照组兔IgG则不能与大鼠腹腔肥大细胞结合。大鼠腹腔内肥大细胞免疫组化分析可见细胞膜染色,说明其Fas表达阳性。
第四部分健脾解毒化浊方治疗腹泻型肠易激综合征的临床研究
中药治疗组与西药治疗组腹痛疗效比较,痊愈率分别为57.7% vs 16.0%(PP)与31.0% vs 7.1%(ITT),总有效率分别为92.3% vs 44.0%(PP)与82.7% vs 39.3%(ITT),两组比较腹痛疗效差异有统计学意义(P均<0.05),说明解毒化浊健脾方改善腹痛疗效优于西药治疗组;腹泻疗效比较,中药治疗组与西药治疗组痊愈率分别为46.2% vs 20.0%(PP)与41.4% vs 17.2(ITT),总有效率分别为96.2% vs 48.0%(PP)与86.2% vs 42.9%(ITT),两组比较腹泻疗效差异有统计学意义(P均<0.05),表明健脾解毒化浊方改善腹泻疗效优于西药治疗组。止泻起效时间及腹泻缓解时间两组比较差异均无统计学意义(P均>0.05),而中药治疗组腹痛缓解时间则明显短于西药治疗组(7.6±4.6d vs 14.4±4.3d, P=0.0125)。中医证侯疗效中药治疗组与西药治疗组中医证侯积分比较差异有统计学意义(7.1±4.6 vs 12.9±6.4, P<0.05),中药治疗组与西药治疗组痊愈率分别为30.8%和4.0%(PP)与27.6% vs 3.6%(ITT),总有效率分别为92.3% vs 48.0%(PP)与82.7% vs 42.9%(ITT),两组比较中医证侯疗效差异有统计学意义(P均<0.05),表明解毒化浊健脾方改善中医证侯疗效优于西药治疗组。中药治疗组腹痛程度、腹痛频率、腹痛持续时间、大便稀溏及大便频率等中医主症均较西药治疗组有明显改善(P均<0.05)。中药治疗组中医伴随症状变化除“情绪紧张等时泻泄加重”及“粘液便”外,“排便急迫或坠胀感”、“胸胁或少腹胀闷”、“嗳气”、“食少”等的改善均优于西药治疗组(P均<0.05)。
结论
1.采用醋酸结肠慢性刺激法可造成稳定的肠道高敏感性IBS大鼠模型;
2.健脾解毒化浊方能降低IBS模型大鼠血清5-HT、血浆SP含量,增加CGRP含量,大剂量健脾解毒化浊方疗效优于得舒特。
3.健脾解毒化浊方的作用机制可能是通过降低模型大鼠血清5-HT、血浆SP含量,减弱背角神经元兴奋性,提高内脏痛阈,消除肠道过敏,从而达到治疗目的。
4.健脾解毒化浊方是通过抑制肥大细胞Ca2+的内流,从而避免了肥大细胞的活化,继而抑制了肥大细胞的脱颗粒作用,减少肥大细胞内组胺等介质的释放,以降低血清中组胺等介质含量,减弱背角神经元兴奋性,从而提高内脏痛阈,消除肠道过敏症状。
5.健脾解毒化浊方抑制大鼠腹腔肥大细胞脱颗粒的分子生物学机制可能是通过促进大鼠腹腔肥大细胞膜表面TLR2与TSP-2结合,并通过Fas途径,促进大鼠肥大腹腔细胞表面过表达Fas,使其与抗大鼠Fas多克隆抗体相结合,从而促进和直接诱导大鼠腹腔肥大细胞凋亡。
6.解毒化浊健脾方不仅仅在于具有解毒化浊、舒肝健脾、清热燥湿之功效,还能调节免疫功能,改善微循环,清除氧自由基,抑制炎症反应、镇痛等多项作用。可见,解毒化浊健脾方治疗IBS是多方面、多环节、综合作用的结果。
Objective: The irritable bowel syndrome (IBS) were one kind of intestinal irritable disease because of intestinal hypersensitivity, is refers to a group of the functionality intestines disorder syndrome including the abdominal pain, the distension of the abdomen, the diarrhea, which of causes and the mechanism is not yet expounded until now.Speeds up unceasingly along with the rhythm of life with the social competition intensely, the incidence of IBS of world is rising day by day, which has interfered with people's normal work, the study and the life seriously.
The IBS cause of disease and the pathogenesis not yet expounded until now.At present we thought that the enhancement of internal organs sensitivity is one of IBS most important pathology physiology characteristics, which is he foundation and symptom diversification reason which the IBS patient symptom produces.In recent years many studies tell us that the mast cell play a critical role during the the pathology and physiological process of intestinal irritable disease. After being activated, the mast cell might release many biological activity different mediums, which release may further enlarge each physiology and pathological reaction, which thus can caused various symptoms.Therefore, suppressing activation of the intestinal mast cell, causing its reduced medium, including histamine, P material quantities, and so on, is the key to treats the intestinal irritable disease.
The pathogenesis of IBS is complex, involving many aspects, including the spirit, the diet, individual quality, and so on. The sole medicine clinical function is usually limit, which cannot satisfy the clinical request.The Chinese Traditional Medicine also believed that, the origin reasons the abdominal pain and diarrhea are complex, while the the laws of treating are also many. Jianpijieduhuazhuofang(JPJDHZF) is a classics Chinese Traditional Medical prescription by famous Chinese Traditional Medical expert Professor Li Diangui, which summarizes after many year clinical practices, is composed of pulsatilla root, goldthread root, scutellaria root, ginseng, astragalus root, white peony root, bighead, tangerine peel, ledebouriella root, ash bark, flavescent sophora root, sanguisorba root, aucklandia root, coix seed, chinese angelica root, liquorice, etc, has the may effections, including removing the poisonous quality of any substance, relieving the depressed liver and invigorating the spleen, reducing fever and remove dampness. Through the long-term clinical observation, it has been proved to have good curative effect on IBS. In order to further probe into the pharmacological action mechanism of JPJDHZF in treating IBS, we embarks from the Pharmacology research, taking the mast cell function research as the key point, applying the verious medhods, including blood biochemistry, the medicine serology, the immunity histochemistry, extriinsic cell culture, as well as the molecular biology method, separately observe IBS rat model behavior, the electricity physiology target, and the blood biochemistry, the phenomenon of degranulation of abnorminal mast cell taken from the rat, as well as the surface antibodyon the abdominal mast cell of the rat, attempts discussesing the effect and action mechanism of JPJDHZfang on IBS from three aspects, including the organ level, the cell level and the gene level, as well as the clinical practical application curative effect research, to provide scientfic basis for giving play to superiority of multi-ways, the multi-targets and the whole treatment of Chinese troditional Medicine, and to exploit and utilize scitificly Chinese troditional Medicine, simultaneously to build the foundation for the new medicine development.
Method
PartⅠ: The Experimental Study on Effect and Mechanism of JPJDHZF on visceral hypersensitivity Rat Model of IBS
Tests one: To apply the acetic acid chronic stimulation in colon to manufacture visceral hypersensitivity Rat Model of IBS. The rats were divided into three groups: the childhood rat acetic acid chronic stimulation group (the NA group), the grown-up rat colon acetic acid chronic stimulation group (the AA group) and the blank control group (the NS group).After modeiiing, the visceral sensitivity measurement were carried on separately to each group of IBS rat model, which conclude the capability limens of the sacculus that caused abdomen-uplifting and back-arching and the time of contract of abdomen muscle in rats, to confirm the succeeds of model.
Tests two: To discuss the effect and Mechanism of JPJDHZF on visceral hypersensitivity rat model of IBS. After have maken the rat model successfull, the rats were divided into the normal control group (A group), the model control group (B group), the dicetel control group (Group C), the low dosage of JPJDHZF group (Group D), the high dosage of JPJDHZF group (Group E). Different groups were received oral administration of different treatment for one month. The capability limens of the sacculus that caused abdomen-uplifting and back-arching and the time of contract of abdomen muscle in rats were observed. The levels of 5-hydroxytryptamine (5-HT), substance P (SP), and calcitonin gene related peptide (CGRP) were evaluated. PartⅡ: The Influence of Drug Serum of JPJDHZF on Degranulation of Peritoneal Mast Cell in Rats Activated by Antigen
At first, the peritoneal mast cell suspension was prepared and was carried on the appraisal.Simultaneously the drug serum of JPJDHZF, the drug serum of cromolyn sodium and the drug serum of bland control group were prepared separately. The experiment was divided into four groups: the high dosage of drug serum of JPJDHZF group, the low dosage of drug serum of JPJDHZF group, the drug serum of cromolyn sodium group, positive control group, and normal control group. The fluorescent Ca2+ indicator Fluo-3 was used to observe and quantitate the effect of JPJDHZF on degranulation percentage, intracellsula[rCa2+]of peritoneal mast cells and histamine release in sensitized rats by confocal laser scan microscope. Simultaneously ,the Influence of Drug Serum of every group on appearance of mast cell, releasing histamine and TNF-α, which degranulated actived by antigen.
PartⅢ: The molecular biology mechanism of JPJDHZF on Restrain Peritoneal Mast Cells from Degranulation
At first, the peritoneal mast cell suspension was prepared and was carried on the appraisal.Simultaneously the drug serum of JPJDHZF, the drug serum of cromolyn sodium and the drug serum of bland control group were prepared separately. The experiment was divided into three groups: the high dosage of drug serum of JPJDHZF group, the low dosage of drug serum of JPJDHZ group, and normal control group. The expressions of TLR2 and the Fas were examines separately in each group of rat abdominal mast cell using the RT-PCR method and the histochemistry colored method. PartⅣ: The Clinical Research About the Effect JPJDHZF on Patients With D-IBS
The prospective, randomized, placebo-controlled, double-blind clinical trial was used. The training was carried on to the participation researcher, about the diagnosis, the integration, and the elimination standards, as well as implementation plan. 137 D-IBS patients were enrolled in this clinical trail from December, 2004 to December, 2006, entering the JPJDHZF treatment group and the western medicine treatment group by 1:1 proportion according to the random digit.The JPJDHZF treatment group takes orally JPJDHZF, the western medicine treatment group takes orally dictel.The observation projects include the situation of abdominal pain and the excrement, the other symptoms which had to be observed still include the felling of urgent or gravistatic defecation, the chest coerced or the lower abdomen abdominal bloating, the mood tight or despondent angry when flows swiftly releases the aggravation situation, the mucus then, belches as well as the feed quantity and so on; Symptom examination including colon area tenderness and tongue and pulse condition.Before the treatment and after 3 weeks of stopping the the treatment, the urine and the feces convention, hepatorenal inspections and electrocardiogram were examined. The close observation included bad event and bad respondence, recording the time when it occured, the performance which it takes, and the processing which we takes, and the result. We should pays attention to the serious bad event and bad respondence.
Result
PartⅠ: The Experimental Study on Effect and Mechanism of JPJDHZF on visceral hypersensitivity Rat Model of IBS Tests one: In the 6th week of modelling, The capability limens of the
AWR that cause abdomen-uplifting and back-arching of NS group are (0.70±0.10)ml and (0.94±0.16)ml, The capability limens of the AWR that cause abdomen-uplifting and back-arching of AA group are (0.76±0.06)ml and (1.02±0.88)ml, There is no difference between them (P>0.05). Those of NA group are respectively (0.43±0.06)ml and (0.61±0.08)ml, which is significant lower than other two groups (P<0.01); When being tested in capacity of 0.5ml, the phenomenon of contract of abdomen muscle in rats of NS group and the AA group is not obvious, but the times of contract of abdomen muscle in rats of the NA group rat reached (6.63±1.06) time /5min, There is significantly different among them (P<0.01). When being tested in capacity of 0.8ml, the times of contract of abdomen muscle in rats of the NA group were more than other two groups obviously (P<0.05). When being tested in capacity of 0.8ml, the times of contract of abdomen muscle in rats of the NA group were more than NS group obviously (P<0.05), while there is no difference does not have the significance between the NA group and the AA group (P>0.05).
Tests two: In the aspect of behavior test, there is significantly different between the B group and A group in the capability limens of the AWR that cause abdomen-uplifting and back-arching after the medication (P<0.01, P<0.05), and there is no difference between the A group and other three groups (P>0.05); there is no remarkable difference among D group, E group and C group (P>0.05); The result of abdominal myo-electricity showed that, when being tested in capacity of 1.0ml and 1.5ml, the times of contract of abdomen muscle in rats of the B group were more than A groups obviously (P<0.01) after the medication. While there is no difference among D group, E group and C group and A group (P>0.05); D, E group compare with C group, not remarkable difference (P>0.05); Comparing with the model control group, every group have distinct improvement in behavior and the electricity physiology target; 5-HT and SP drops obviously in each treatment group; The content of CGRP increases than before.
PartⅡ: The Influence of Drug Serum of JPJDHZF on Degranulation of Peritoneal Mast Cell in Rats Activated by Antigen
The degranulation percentage of peritoneal mast cells in high dosage of JPJDHZ group was 13%, which was significantly lower than that of the model control group (65%, p<0.05); There was also significant difference between the low dosage of JPJDHZF group and the model control group(23% vs 65%, p<0.05). The phenomenon of degranulation of mast cells in model control group is more obvious than that of treatment groups. Intracellsular[Ca2+]of peritoneal mast cells of high dosage of JPJDHZF group was significantly lower than that of control group (48.74±5.43nmol/L vs 436.16±12.30nmol/L, p<0.05); The histamine concentration of high dosage of JPJDHZF group was significantly lower than that of control group (33.23±21.50nmol/L vs 98.41±7.23nmol/L , p<0.05).
PartⅢ: The molecular biology mechanism of JPJDHZF on Restrain Peritoneal Mast Cells from Degranulation
The result showed that, the ratio of TLR2mRNA/βactinmRNA and the ratio of FasmRNA/βactinmRNA of peritoneal mast cells in both the high-dosage of JPJDHZF group and the low-dosage of JPJDHZF group were higher than those of normal control group after they are stimulated by drug serum of JPJDHZF for 30min (P<0.05), which is confirmed that the drug blood serum can stimulate the expression of TLR2mRNA and FasmRNA; The effect of high-dosage of JPJDHZF group was most obvious, with the significance difference with the control group (P<0.05).
The result of the immunohistochemical experiment showed that TSP-2 could combine with peritoneal mast cells of rats; While rabbit IgG of control group cannot combine with peritoneal mast cells of rats. The membrane of peritoneal mast cells were stainned, which were explained that the expression of Fas is positive..
PartⅣ: The Clinical Research About the Effect JPJDHZF on Patients With D-IBS
The cure rate of JPJDHZF on abdominal pain in patients with D-IBS is better than that of dicetel [57.7% vs 16.0%(PP), 31.0% vs 7.1%(ITT)]; The effective rate of JPJDHZF on abdominal in patients with D-IBS is also better than that of dicetel [92.3% vs 44.0%(PP)与82.7% vs 39.3%(ITT)], which shows that there is significant difference between them (P<0.05). The cure rate of JPJDHZF on diarrhea in patients with D-IBS is better than that of dicetel [46.2% vs 20.0% (PP), 41.4% vs 17.2 (ITT)]; The effective rate of JPJDHZF on abdominal in patients with D-IBS is also better than that of dicetel [96.2% vs 48.0%(PP)与86.2% vs 42.9% (ITT)], which shows that there is significant difference between them (P<0.05). There were no difference in both the antidiarrhea time and analgesic time between the two groups (P>0.05).
The cure rate of JPJDHZF group on syndrome of TCM in patients with D-IBS is better than that of dicetel group [30.8% vs 4.0%(PP), 27.6% vs 3.6%(ITT)]; The effective rate of JPJDHZF on abdominal in patients with D-IBS is also better than that of dicetel [92.3% vs 48.0%(PP), 82.7% vs 42.9%(ITT)], which shows that there is significant difference between them (P<0.05). There are more development in JPJDHZF group with the degree of abdominal pain, the frequence of abdominal pain, the time of abdominal pain, etc, which are better than those of dicetel group (P<0.05). There are more development in JPJDHZF group with concomitant symptom of syndrome of TCM, which including eructation, anorexia, abnorminal distension, tenesmus, than those of dicetel group (P<0.05).
Conclusions
⒈Visceral hypersensitivity Rat Model of IBS which was manufactured by the acetic acid chronic stimulation in colon is steady and practicable.
⒉JPJDHZF could lower the level of 5-HT and SP, and increase CGRP of IBS model rats, especially high dosage of JPJDHZfang.
⒊The mechanism of JPJDHZF may be increasing the limen of pain of bowel, eliminating hypersusceptibility of bowel, and decreasing excitability of nerve cells by decreasing the contents of 5-HT and SP in IBS model rats.
⒋JPJDHZF can avoid being activated of mast cells by inhibiting entering of Ca2+, thus it has obvious inhibitory effect on degranulation and histamine releasing of peritoneal mast cells in sensitized rats, which can reduce the content of histamine in the serum, raise threshold of pain, and eliminate the symptom of intestinal irritability.
⒌The molecular biology mechanism of JPJDHZF on restrain peritoneal mast cells from degranulation is promote and induce the depression of mast cell directly by the combination of TLR2 and TSP-2 and the expression of Fas on the surface of peritoneal mast cells of rats.
⒍JPJDHZF has the may effections, including not only removing the poisonous quality of any substance, relieving the depressed liver and invigorating the spleen, reducing fever and remove dampness, but also improving the function of immunity and microcirculation, elimilating the free radical, inhibiting the inflammatory reaction, and relieving pain. It has superiority of multi-ways, the multi-targets and the whole treatment of Chinese troditional Medicine to treat with IBS.
引文
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