【作者】 刘珊珊；

【导师】 王汝俊；

【作者基本信息】 广州中医药大学 ， 中西医结合基础， 2006， 硕士

【摘要】 肠易激综合征是基于肠道高敏感性和高反应性基础上的功能异常。其病因及发病机制复杂,涉及多系统,现代医学以对症治疗为主,目前仍缺少理想的疗法和药物。近期研究较多的选择性5—羟色胺受体调节剂可改善IBS多个症状,但由于其副作用而限制了临床应用。中药具有多靶点、整体调节及副作用小的优势。而且从国内的临床疗效报道来看,中医治疗效果明显优于西医治疗。本病的中医临床分型各家报道不一,但肝郁脾虚型是该病临床表现最多的证型之一,治疗多采用舒肝健脾理气法。舒肝健脾复方系本研究所临床经验方,治疗肝郁脾虚型肠易激综合征多获得良效。 本课题从IBS大鼠内脏高敏感性动物模型的复制入手,建立适用于中医药研究的IBS大鼠模型,在此基础上探讨舒肝健脾复方对实验性肠易激综合征的治疗作用和作用机制。研究不仅为临床用药、新药开发提供实验依据,而且对探讨中医治疗IBS的治法理论也具有重要意义。 1 IBS动物模型的复制 取出生后8—21d的大鼠,模型组每天给予直肠内醋酸刺激,复制内脏高敏感大鼠模型,正常组给等量生理盐水。分别在出生后6周及8周进行直肠扩张,评估其腹部收缩反射(AWR)阈值;并测定致痉剂作用于模型大鼠离体肠管舒缩运动的升高幅度。结果显示与正常组相比,直肠扩张时,模型组大鼠腹部抬高和背部拱起的压力阈值显著降低(P<0.01);离体肠管在加入致痉剂后模型组升高值均明显大于正常组(P<0.01)。提示新生期肠道内的慢性炎症刺激,可以在成年后引起慢性内脏敏感性增高,模型大鼠的离体小肠对致痉剂的反应性增高。 2 舒肝健脾复方对IBS模型大鼠的治疗作用 将五窝新生SD大鼠随机分为正常组、模型组、中药低剂量组、中药高剂量组、泽马可组,后四组从第8—21天,每天给予直肠内醋酸刺激,复制内脏高敏感大鼠模型,分别在出生后第6周及8周进行直肠扩张,评估其腹部收缩反射(AWR)阈值;8周后,分别给予蒸馏水、生理盐水、舒肝健脾复方5g/kg、舒肝健脾复方10g/kg、泽马可4mg/kg灌胃,每日一次,共两周,治疗后再次评估其腹部收缩反更多还原

【Abstract】 Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility. Recent studies indicated that the pathogeny of IBS was complex and involved with multisysterm. Due to be short of ideal therapy and drug, symptomatic treatment is the primary treatment at present. Selective 5-hydroxytryptamine receptor conditioners could improve some symptoms of IBS, but were limited in clinic because of their side effects. Multi-target, integrity effect and few side effects are superiority of traditional Chinese medicine (TCM).The clinical reports showed that curative effect of TCM was superior to that of Western medicine. Stagnation of liver-energy and asthenia of spleen was one of the most common types and was treated by the therapy of comfortable liver strengthen spleen. The Shugan Jianpi (SJ) Decoction is frequently used in PiWei institute to treat IBS.To investigate the effect and mechanism of SJ Decoction, the model of chronic visceral hypersensitivity was established which adapted to the study of traditional Chinese medicine. The investigation could not only provide experimental proof of guiding clinical medication and developing new medicine, but also conduce to study the treatment of IBS with TCM. 1 Replicate the model of IBSIn order to replicate the model of chronic visceral hypersensitivity in adult rats, SD rats of the model group were given acetic acid in rectum every day between postnatal 8d and 21d. Rats of the normal group were given normal saline. Then the threshold of abdominal withdrawal reflex (AWR) was measured at 6w and 8w with rectal distension and the amplification of movement in isolated rat’ intestine caused by Ach or 5-HT was tested. The threshold of abdomen lifting and body arching of the model group showed a obvious decrease compared with the normal group(P<0.01). The amplification of movement in isolated intestine of model rat stimulated by Ach or 5-HT was greater than that of normal group (P<0.01). Chronic colon irritation in neonatal rats leaded to a state of chronic visceral hypersensitivity toadult rats. The isolated intestine of the model rats had high responsiveness.2 Effect of SJ decoction on the model of IBSFive litters of neonate rats were divided into five groups at random, followed by normal group, model group, SJ decoction low dose (SJL) group, SJ decoction high dose (SJH) group, Zelmac group .In order to replicate a model of chronic visceral hypersensitivity, all the rats between postnatal 8d and 21 d were given acetic acid in rectum every day except the normal group which was given saline in rectum every day. Then the threshold of AWR was measured at 6w and 8w during rectal distension. The threshold of abdomen lifting and body arching of normal group showed an obvious increase compared with the other four groups (PO.01). Then the rats were treated with administration of distilled water 25ml/kg, NS 25ml/kg, SJ decoction 5g/kg, SJ decoction lOg/kg, Zelmac 4mg/kg from 9w to lOw. After the treatment the threshold of AWR was measured again. Then the quantity of mast cell of colon was weasured. The content of NO in blood , the content of 5-HT in bloods brain and colon were observed in the experiment. The results showed that the threshold of AWR of SJL and SJH group showed an obvious increase compared with the model group (PO.01, PO.01). The quantity of mast cell of colon of SJH group showed an obvious decrease compared with the model group (P<0.05). The content of NO in blood of SJL and SJH group showed an obvious increase compared with the model group (P<0.05, PO.01). The content of 5-HT in blood of SJH group showed an obvious decrease compared with the model group (P<0.01). Experiment study confirmed: With the effects of S J decoction ,the threshold of AWR and the content of NO in blood could be increased , the quantity of mast cell of colon and the content of 5-HT in blood could be decreased, the content of 5-HT in brain and colon could be decreased to a degree. The SJ decoction showed affirmative curative effect on treating rats of IBS. It could be one of the mechanisms of action to influence the content of NO and 5-HT.3 Effect of SJ decoction on calnK analgesic > antidiarrheaTo investigate the calm> analgesic > antidiarrheal effects of SJ decoction , autonomic activities experiment >. hot-plate experiment and writhing reaction experiment antidiarrhea experiment induced by senna were used. SJ decoction could remarkably reduce the frequency of acetic acid-induced writhing ,delay the time of licking rear feet and could remarkably reduce the frequency of diarrhea .But the change of autonomic activities had no statistical significance. SJ decoction had affirmative analgesic and antidiarrheal effects, which could be the mechanism ofhealing IBS.4 Effect of SJ decoction on gastrointestinal motilityTo investigate the effect of SJ decoction on gastrointestinal motility, the change of intestinal propulsion ratio was observed in vivo.As well as the spontaneous contraction and the antagonistic contraction of intestinal stimulated by Ach , BaCh , 5-HT in vitro. The experiments showed: the intestinal propulsion ratio was remarkably reduced in SJ decoction groups. The spontaneous contraction and the antagonistic contraction of intestinal were dose-dependently inhibited after used the SJ decoction.The conclusion was :SJ decoction had restraining effect on the movement of intestinal tract, which was related to mechanism of action.更多还原