【摘要】： 目的:探討腸易激綜合征(irritable bowel syndrome)的發(fā)病機(jī)制以及痛瀉要方煎劑治療腸易激綜合征內(nèi)臟高敏感性大鼠的機(jī)制。 方法: 1.選用清潔級(jí)新生SD大鼠,采用直腸慢性刺激加夾尾刺激法造模。于大鼠出生后第8-21d,每天給予直腸內(nèi)醋酸刺激,兩周后予急性應(yīng)激夾尾刺激一周,在出生后第7,9,11周對(duì)這些成年后的大鼠進(jìn)行直腸擴(kuò)張,評(píng)估其腹部收縮反射(AWR)閾值,12周測定大鼠腹壁肌電話動(dòng),驗(yàn)證敏感性有無異常改變。證實(shí)造模是否成功。 2.造模成功后,將實(shí)驗(yàn)動(dòng)物分組為中藥低劑量組(A組)、中藥中劑量組(B組)、中藥高劑量組(C組)、西藥奧替溴銨組(D組)、空白對(duì)照組(E組)、模型對(duì)照組(F組)。其中E組為正常大鼠,A、B、C、D、F組為模型大鼠。E組和F組以生理鹽水按4ml/100g(40g/kg/d)灌胃,A、B、C組分別以痛瀉要方煎劑按中藥低劑量組0.4ml/100g(4g/kg/d)、中藥中劑量組1.2ml/100g(12g/kg/d)、中藥高劑量組4ml/100g(40g/kg/d)灌胃,D組西藥奧替溴銨組按4ml/100g(150g/kg/d)灌胃,每天兩次,連續(xù)30天。觀察球囊在各組大鼠腸道內(nèi)擴(kuò)張引起腹部抬起和背部拱起的容量閾值以及球囊在各組大鼠腸道內(nèi)不同容量下擴(kuò)張腹壁收縮次數(shù)。放射免疫法測血漿P物質(zhì)(SP )、結(jié)腸組織勻漿P物質(zhì)(SP )、血漿降鈣素基因相關(guān)肽(CGRP)、結(jié)腸組織勻漿降鈣素基因相關(guān)肽(CGRP)含量。結(jié)果作統(tǒng)計(jì)分析。 結(jié)果: 1.與新生期生理鹽水刺激組(C組)和新生期醋酸刺激組(B組)相比,直腸擴(kuò)張時(shí),新生期醋酸刺激后2周加夾尾刺激組大鼠(A組)腹部抬起和背部拱起的容量閾值顯著降低(P值均0.01);0.3、0.6、0.9 ml擴(kuò)張容量下A組腹壁肌電活動(dòng)明顯增強(qiáng)(與B組相比,P分別均0.05;與C組相比,P分別0.01、0.05和0.05)。2.用藥后,痛瀉要方與斯巴敏都能使腸道致敏后所致的行為學(xué)與電生理指標(biāo)恢復(fù)正常,且中藥高劑量組與斯巴敏組組間無差異。而中藥低劑量組和中劑量組使腸道致敏后所致的行為學(xué)與電生理指標(biāo)恢復(fù)不明顯,沒有達(dá)到統(tǒng)計(jì)學(xué)意義。模型大鼠血清SP含量明顯增加,痛瀉要方高劑量組與西藥斯巴敏組都能使模型大鼠血清SP含量明顯回落,且中藥高劑量組與斯巴敏組組間無差異。模型大鼠結(jié)腸粘膜SP含量明顯增加,痛瀉要方中、高劑量組與西藥斯巴敏組都能使模型大鼠結(jié)腸粘膜SP含量明顯回落,且中藥中、高劑量組與斯巴敏組間無差異。痛瀉要方高劑量組能顯著增加血漿和結(jié)腸組織CGRP含量,痛瀉要方低劑量組、中劑量組與西藥組均不能。 結(jié)論: 1.新生期大鼠腸道內(nèi)的慢性刺激加夾尾刺激可以在成年后引起慢性內(nèi)臟敏感性增高。并表明應(yīng)激和腸道感染兩因素共同作用時(shí)具有致腸動(dòng)力紊亂的協(xié)同效果,應(yīng)激使感染后的腸道易于發(fā)生動(dòng)力紊亂,已被感染過的腸道對(duì)應(yīng)激的反應(yīng)更為強(qiáng)烈。而腸粘膜未見異常病理改變,符合IBS的基本特征。 2.痛瀉要方煎劑能使腸道致敏后所致的行為學(xué)與電生理指標(biāo)恢復(fù)正常,SP含量上升在IBS發(fā)病機(jī)制中起重要作用,IBS能導(dǎo)致血漿和結(jié)腸組織中CGRP含量下降。痛瀉要方能降低模型大鼠血漿和結(jié)腸組織SP含量,增加CGRP含量,而斯巴敏僅能降低SP含量。本方的作用機(jī)制可能是通過降低模型大鼠血漿和結(jié)腸組織SP含量,減弱背角神經(jīng)元興奮性,從而提高內(nèi)臟痛閾,消除腸道過敏。綜合起來看,痛瀉要方高劑量組的療效優(yōu)于斯巴敏。
[Abstract]:Objective: To investigate the pathogenesis of irritable bowel syndrome and the mechanism of Tongxieyaofang Decoction in treating visceral hypersensitivity rats with irritable bowel syndrome.
Method:
1. Neonatal SD rats of clean grade were selected and modeled by rectal chronic stimulation plus tail clamping stimulation. The rats were given intrarectal acetic acid stimulation every day for 8-21 days after birth, followed by acute stress tail clamping stimulation for one week, rectal dilatation was performed at 7, 9 and 11 weeks after birth, and the abdominal systolic reflex (AWR) threshold was assessed for 12 weeks. The abnormality of the sensitivity of the abdominal wall muscles in rats was tested.
2. After successful modeling, the experimental animals were divided into low-dose group (group A), middle-dose group (group B), high-dose group (group C), Otibromide group (group D), blank control group (group E), model control group (group F). Group E was normal rats, group A, B, C, D, F were model rats. Group E and F were given normal saline 4 ml/100 g (40 g/kg/d), and group A, B, C, D, F were given orally. Group B and group C were given Tongxie Yaofang Decoction 0.4ml/100g (4g/kg/d) in low dose group, 1.2ml/100g (12g/kg/d) in middle dose group, 4ml/100g (40g/kg/d) in high dose group, and Otibromide group D was given Otibromide Decoction 4 ml/100g (150g/kg/d) twice a day for 30 days. Volume threshold of dorsal arch and contraction times of abdominal wall dilated by balloon in different intestinal volumes of rats were measured by radioimmunoassay. The contents of substance P (SP), substance P (SP) in plasma, calcitonin gene-related peptide (CGRP) in colon tissue homogenate, and calcitonin gene-related peptide (CGRP) in plasma were measured.
Result:
1. Compared with the neonatal saline stimulation group (group C) and neonatal acetic acid stimulation group (group B), the volume threshold of abdominal elevation and dorsal arch in neonatal acetic acid stimulation group (group A) decreased significantly 2 weeks after rectal dilatation (P 0.01); the abdominal myoelectric activity in group A increased significantly (compared with group B) at 0.3, 0.6, 0.9 ml dilatation volume. Compared with C group, P was 0.05, P was 0.01, 0.05 and 0.05). 2. After treatment, both Tongxie Yaofang and Spasmone could restore the normal behavior and electrophysiological indexes caused by intestinal sensitization, and there was no difference between high dose group and Spasmone group. There was no significant difference in the recovery of physiological indexes between the two groups. The content of SP in the colon mucosa of the model rats increased significantly, and the content of SP in the high dose group of Tongxie Yaofang and the western medicine Spamin group decreased significantly. The high dose group of Tongxie Yaofang could significantly increase the content of CGRP in plasma and colon tissue, while the low dose group of Tongxie Yaofang could not.
Conclusion:
1. Chronic intestinal stimulation plus tail clip stimulation in neonatal rats can increase the sensitivity of chronic viscera in adulthood. It shows that stress and intestinal infection have synergistic effects on intestinal motility disorder. Stress makes the infected intestine prone to dynamic disorder, and the infected intestine is more responsive to stress. There was no abnormal pathological changes in intestinal mucosa, which accords with the basic characteristics of IBS.
2. Tongxie Yaofang Decoction can restore the behavioral and electrophysiological indexes induced by intestinal sensitization. The increase of SP content plays an important role in the pathogenesis of IBS. IBS can lead to the decrease of CGRP content in plasma and colon tissues. Tongxie Yaofang Decoction can decrease the SP content in plasma and colon tissues of model rats, increase the CGRP content, while Spasmone can only decrease the S content. The mechanism of action of Tongxie Yaofang may be that it can increase visceral pain threshold and eliminate intestinal allergy by lowering SP content in plasma and colon tissue of model rats and decreasing the excitability of dorsal horn neurons.
【學(xué)位授予單位】：遼寧中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R-332;R285.5

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