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加味二至煎治疗便秘型肠易激综合征的临床与实验研究
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摘要
第一部分临床研究
     目的:观察加味二至煎治疗便秘型肠易激综合征(Irritable Bowel Syndrome,IBS)肠燥热结证的临床疗效及对生活质量的影响。
     方法:采用随机对照法。将符合纳入标准的病例80例按“随机数字表法”随机分为治疗组和对照组,治疗组40例,对照组40例,治疗组服用加味二至煎汤剂,对照组服用复方芦荟胶囊,两组均服药4周。观察治疗前后便秘型IBS主要症状改善情况,生活质量影响,远期疗效及不良反应。
     结果:(1)临床症状疗效:治疗后治疗组临床症状总有效率87.50%,对照组84.21%。两组比较,无差异(P>0.05)。(2)治疗前后主要症状积分比较:在治疗2周后,治疗组各症状均比治疗前有改善(均P<0.05),而对照组只在大便性状、排便困难、腹胀和腹痛症状方面比治疗前有改善(均P<0.05);在治疗4周后治疗组各症状均较治疗前显着改善(均P<0.01),且较治疗2周后有差异(均P<0.05),而对照组各症状均较治疗前有改善(均P<0.05),但较治疗2周后无差异。改善大便性状、腹痛、排便困难、精神方面等症状上治疗后治疗组与对照组比较有差异(均P<0.05)。(3)治疗前后生活质量各观察指标积分比较:两组生活质量积分均比治疗前改善,有差异(P<0.01或P<0.05);(4)远期疗效对比:治疗组复发率为9.4%,对照组为36.7%,两组比较有差异(P<0.05)。(5)两组治疗安全性评估:治疗前后两组病人血、尿、便常规,心电图、肝肾功能均无明显变化,提示治疗组和对照组均无明显的毒副作用。
     结论:临床研究表明,加味二至煎治疗便秘型IBS肠燥热结证能改善其临床症状,提高生活质量,降低复发率,其疗效作用优于复方芦荟胶囊对照组。研究结果从临床角度验证了加味二至煎治疗便秘型IBS的实用性和可行性。
     第二部分实验研究
     目的:探讨加味二至煎治疗便秘型肠易激综合征动物模型的作用机制,为临床研究提供实验依据。
     方法:根据随机数字表将40只Wistar雌雄各半大鼠随机分为5组:正常对照组(即空白组)、模型组、西沙比利组、复方芦荟胶囊组、中药治疗组,每组8只。除正常组外,其余各组大鼠均采用冰水灌胃法造模。造模成功后第二天开始治疗:中药治疗组按23.7g生药/kg体重每日灌胃加味二至煎汤剂1次;西沙比利组按30mg/kg每日灌服西沙比利1次;复方芦荟胶囊组按20mg/kg每日灌服复方芦荟胶囊;正常组、模型组每日灌胃等容积的生理盐水;每组均连续灌胃14天。治疗前后记录各组大鼠粪便粒数及含水量,体重变化。末次给药后禁食不禁水10小时,后用50%墨汁灌胃(1ml/只),20min后断头处死,留取肠标本做以下指标测定:小肠碳末推进率、结肠(距肛门5cm)组织内血管活性肠肽(VIP)、小肠组织内神经肽P物质(SP)、局部肠组织病理观察。
     结果:(1)各组大鼠治疗前后粪便粒数及含水量比较:模型组、西沙比利组、中药治疗组、复方芦荟胶囊组治疗前1天粪便粒数及含水量均明显低于正常组(P<0.01);中药治疗组治疗后第14天粪便粒数及含水量高于西沙必利组(P<0.05),与复方芦荟胶囊组比较无明显差异(P>0.05),(2)各组大鼠体重变化:与正常组比较,造模后其它各组大鼠体重均有所增重(P<0.05);治疗后,与正常组比较,模型组大鼠体重增重明显(P<0.05),其余各组比较无显着性差异(P>0.05)。(3)小肠碳末推进率比较:与正常组相比,模型组、西沙比利组、复方芦荟胶囊组碳末推进率明显降低(P<0.01),以模型组最明显;中药治疗组与正常组无明显差异(P>0.05)。(4)各组大鼠结肠粘膜组织中VIP含量变化:西沙比利组、复方芦荟胶囊组、中药治疗组结肠粘膜组织中VIP含量较模型组显着增加(P<0.05),以中药治疗组最明显(P<0.01)。(5)各组大鼠小肠粘膜组织中SP含量变化:中药治疗组及复方芦荟胶囊组小肠粘膜组织中SP含量较模型组明显增加(P<0.01);与西沙比利组相比,中药治疗组粘膜组织中SP含量明显增加(P<0.05)。(6)各组大鼠局部肠组织病理检查:各组大鼠肠粘膜均未见有明显的炎性病变。
     结论:加味二至煎可能是通过调整紊乱的SP、VIP等胃肠激素分泌、释放来达到治疗肠易激综合征的目的。
The first department
     Objective: To observe the clinical curative effect of treating constipation predominant irritable bowel syndrome with Jiawei Erzhi Jian and the influence of quality of life.
     Method: The case-control study was adopted. The selected cases according to“Randomized Number Scale”were randomly divided into two groups: 40 patients in treatment group were administered with Jiawei Erzhi Jian; 40 patients in control group were administered with Compound prescription aloe capsule. Both groups were treated for four weeks. Clinical symptoms’changes, effect on quality of life before and after treatment were detected respectively to evaluate the therapeutic effects.
     Result:(1)Clinical symptom therapeutic effect: In treatment group the total efficiency is 87.50%,which is no significantly difference than that of control group(P>0.05).In control group the total efficiency is 84.21%. (2) Compared the main clinical symptom before and after treatment: After treats 2 weeks,all the main clinical symptoms were improved after treatment in treatment group(P<0.05), while only bowel movement character, bowel movement difficulty, distension of the abdomen and abdominal pain were improved after treatment in control group (P<0.05); After treats 4 weeks , all the main clinical symptoms were markedly improved after treatment in treatment group(P<0.01), and after also treats 2 weeks to have the difference (P<0.05) before, but the control group various symptoms treat have the improvement (P<0.05), but after treats 2 weeks the difference not to be remarkable. There was a significantly difference between treatment group and control group after treatment in bowel movement character, abdominal pain, bowel movement difficult, energetic aspect(P<0.05). (3) Compared the observation indexs of quality of life before and after treatment: After treatment two group of quality of life integral compared to before treatment remarkable improvement, has the remarkable different significance (P<0.01 or P<0.05 ) (4)Compared prostecdtive efficacy:The recurrence rate in treatment group was 9.4% while in control group was 36.7%.There was a significantly difference between two groups(P<0.05).(5)Evaluate therapeutic safety in the two groups: There were neither obvious changes in blood, urine or stool rules before and after treatment nor in Electrocardiogram or liver-renal function. In the course of the treatment, all patients had no undesirable response, which pointed the fact that treatment group and control group have no toxic and side effect.
     Conclusion: The study indicates that Jiawei Erzhi Jian can improve patient’s clinical symptom, sublimate quality of life, decrease the recurrence rate of constipation predominant Irritable Bowel Syndrome. Its curative effect is better than that of Compound prescription aloe capsule. The research from clinical curative effective aspect approves that Jiawei Erzhi Jian is feasible and practicable in treating constipation predominant Irritable Bowel Syndrome.
     The Second Department
     Objective: To explore mechanism of Jiawei Erzhi Jian in treating constipation predominant irritable bowel syndrome by constructing animal model.The aim is to provide experimental evidence for clinical research.
     Method: 40 healthy half and half female and male Wistar rats were selected and randomly divided into five groups:normal group, Cisapride group, model group ,Compound prescription aloe capsule group, traditional Chinese medicine treatment group , each group had 8 rats. Besides the normal group, other each group of rats use method of the ice water to fill the stomach law to make rat models of constipation predominant irritable bowel syndrome . After making the mold succeeds, the second day to start to treat: the amount of dried medicinal herb given to traditional Chinese medicine treatment group was 27.3g/kg weight . The amount of Cisapride given to Cisapride group was 30mg/kg weight. The amount of Compound prescription aloe capsule given to Compound prescription aloe capsule group was 20mg/kg weight. The normal saline was given to normal group and model group, respectively.Each group continuously fills the stomach 14 days. Excrement number of seeds and water content, body weight change were observed before and after treatment. After end time for medicine, fasts to be unable to restrain the water 10 hours, Two weeks later ,50% charcoal suspension lavaged, all rats were killed to observe following index after 20 min:small intestine charcoal suspension pushing rate,vasoaction intestinal ploypeptide(VIP),substance P(SP), pathology of bowel mucosa tissue.
     Result:(1) Compared excrement number of seeds and water content before and after treatment: excrement number of seeds and water content before one day treatment in model group,Cisapride group, Compound prescription aloe capsule group, traditional Chinese medicine treatment group was markedly lower than that of normal group(P<0.01).After fourteen day treatment in traditional Chinese medicine treatment group was markedly higher than that of Cisapride group(P<0.01) ,but it and compound prescription aloe capsule group was no significant difference(P>0.05),(2) The change in body weight: Compared with normal group,the body weight of other rat groups was all weiht after model (P<0.01).Compared with normal group, the body weight of model group was markedly weight after treatment (P<0.01). There were no significantly difference among the rest groups.(3)Compared the small intestine charcoal suspension pushing rate:Compared with normal group, model group,Cisapride group and compound prescription aloe capsule group could decrease charcoal suspension pushing rate(P<0.01), especially model group. There were no significantly difference between traditional Chinese medicine treatment group and normal group.(P>0.05) (4) The contents of VIP in colon mucous membrane organization: Contents of VIP in Cisapride group and compound prescription aloe capsule group and traditional Chinese medicine treatment group was markedly increased than that of model group, especially traditional Chinese medicine treatment group. (5) The contents of SP in Small intestine mucous membrane organization : Contents of SP in traditional Chinese medicine treatment group and compound prescription aloe capsule group was markedly increased than that of model group(P<0.01). Compared with Cisapride group, traditional Chinese medicine treatment group could significant increase the Contents of SP (P<0.05). (6)Observation of bowels mucosa tissue:The bowels mucosa tissue of rats was not found apparente inflammatory pathological changes。
     Conclusion: The mechanism of Jiawei Erzhi Jian in the treatment of IBS was to adjust the disordered secretion and release of gastrointestinal hormones,such as VIP, SP
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