【作者】 肖政华；

【导师】 刘柏炎；

【作者基本信息】 湖南中医药大学 ， 中西医结合内科学， 2012， 博士

【摘要】 1目的探讨四磨汤对餐后不适综合征(肝脾气滞证)FD患者的临床疗效、心理量表评分及血浆Ghrelin的影响；同时,观察四磨汤对慢性应激小鼠胃肠功能、胃肠道和脑区Ghrelin及其受体表达的影响,以期为中医肝脾相关理论的现代生物学基础是脑肠轴失衡的假说,寻找临床和实验依据。2方法2.1应用随机、双盲、双模拟法,选取餐后不适综合征FD患者(中医诊断为肝脾气滞证痞满者),予四磨汤治疗,观察治疗前后患者症状、胃肠排空功能、血浆Ghrelin水平及SAS、SDS评分变化情况,评价其疗效。2.2采取不可预知的慢性应激法制备胃肠功能障碍小鼠模型,予四磨汤干预,观察治疗前后模型小鼠的一般状况、饮食量、体重的变化,研究四磨汤对模型小鼠胃排空率、小肠推进率和胃动素、胃泌素、胃肠道和脑区Ghrelin及其受体mRNA表达的影响。3结果3.1临床研究两组患者总有效率比较差异无统计学意义(P>0.05)。但总显效率治疗组优于对照组(P<0.05)。证候中的嗳气反酸、心烦易怒,喜叹息,便秘的症状疗效,治疗组优于对照组(P<0.05)。两组患者胃排空率及血浆Ghrelin水平均明显提高,两组之间无显著性差异(P>0.05)。治疗组治疗后Ghrelin水平与正常组比较(P<0.05),而对照组治疗后与正常组比较仍明显减低(P<0.01)。FD患者中,伴有焦虑症状者占31.67%,伴有抑郁症状者占25%。FD患者的SAS、SDS评分与我国常模比较均明显升高(P<0.01)。FD病情重度者伴焦虑、抑郁的人数明显高于病情中度者(P<0.01)。四磨汤可以降低患者SAS、SDS评分,两组之间比较没有统计学意义(P>0.05),但治疗组治疗后SAS标准分与治疗前比较P<0.05。3.2实验研究不可预知的慢性应激可使小鼠食量、体重、胃排空率、小肠推进功能明显下降(P<0.01),胃肠组织无明显病理改变。模型小鼠血清MTL、GAS、Ghrelin含量明显降低(P<0.01),脑、胃、十二指肠Ghrelin及其受体GHSR mRNA的表达明显减少(P<0.01)四磨汤组和多潘立酮组食量、体重均明显增加(P<0.01),胃排空、小肠推进功能均得以恢复(P<0.05),两组血清MTL、GAS、Ghrelin含量均升高(P<0.05),两组之间比较差异无统计学意义(P>0.05)。脑、胃组织中Ghrelin及其受体GHSR mRNA阳性表达方面,四磨汤组与模型组比较显著增多(P<0.01),多潘立酮组与模拟组比较增多(P<0.05)。在十二指肠Ghrelin及其受体GHSR mRNA阳性表达方面,两组与模型组比较均升高(P<0.05)。四磨汤组与多潘立酮组相比,上述指标差异均无统计学意义(P>0.05)。结论1.四磨汤能显著改善餐后不适综合征FD患者的临床症状,促进胃排空,四磨汤组总疗效与多潘立酮组相当。2.FD患者血浆Ghrel in的含量显著降低,并与病情严重程度呈负相关。四磨汤可以调节患者血浆Ghrelin水平,稍优于多潘立酮组。3.FD伴有焦虑、抑郁情况明显高于普通人群,消化不良症状程度与SAS、SDS评分呈正相关。四磨汤可以降低患者SAS、SDS评分,对患者焦虑状况有所改善,但无明显改善抑郁状况的作用。4.四磨汤能促进慢性应激小鼠胃排空率、小肠推进率,增加不可预知慢性应激小鼠食量、体重,能调节血中MTL、GAS、Ghrel in水平及脑、胃、十二指肠Ghrelin及其受体GHSR mRNA的表达。5.四磨汤治疗FD的机制可能是通过调节脑肠肽的水平变化,协调脑肠轴的平衡而实现的,这也为中医肝脾相关理论的现代生物学基础是脑肠轴失衡的假说提供了证据。更多还原

【Abstract】 Objective:To study the clinical curative effect of Simo Decoction on patients with Postprandial distress syndrome of functional dyspepsia.Explore spirit psychological factors and FD relationship,and from brain gut peptide, brain-gut interaction, brain-gut axis imbalances, discusses the mechanism. Simultaneously,to observe how Simo Decoction affect the chronic stress of gastrointestinal function of mice, gastrointestinal tract and Ghrelin and its receptor expression in brain regions.The thesis provide Chinese medicine, liver and spleen related theory of modern biological basis with brain-gut axis imbalances hypothesis, esearching clinical and experimental basis.Methods:1.Patients with postprandial distress syndrome of functional dyspepsia being selected, are randomly divided into treatment group and control group, correspondly given Simo Decoction, and then observe the patients’gastrointestinal emptying-function, symptoms and brain gut peptide, levels of plasma Ghrelin before and after treatment to evaluate their curative effect.2.Applying the model group of gastrointestinal-emptying impediment by the method of unpredictable chronic stress, next,randomly dividing the mice into model group, Simo Decoction group, domperidone group,and then respectively giving different treatment to observe the situation of animals’carbonpowder-promoting,the residual rate in stomach, to examinate the levels of motilin, gastrin, Ghrelin in serum, Ghrelin and GHSR expression in the stomach, brain and small intestine.Results:1. Clinical ResearchIn two groups of patients with total efficiency compare difference not to have statistical significance (P>0.05)。But the markedly effective rate in treatment group than in control group (P<0.05). For the healing effect of the symptoms of belching and acid reflux, restlessness,regular sigh, constipation, the treatment group is superior to control group(P<0.05) there is no statistical significance between the levels of Ghrelin in plasma and gastric evacuation rate (P>0.05).The comparison between the treatment group after being treated and normal group in respect of the level of Ghrelin (P<0.05),after being treated,the control group is markedly deduced,comparing with normal group (P<0.01). FD patients, with anxiety symptoms and depressive symptoms account for31.67%and25%respectively. Compared with China’s general population standard,the grade of SAS and SDS for patients is significantly higher (P<0.01).The number of patients with serious condition accompanying anxiety and depression apparently higher than those with moderate condition. After treatment,the grade of SAS and SDS for patients is decreased and the comparison between the two groups exist no statistical significance (P>0.05). But for the treatment groups, the comparison between after and before treatment in aspect of standard score of SAS P<0.052.Experimental StudyUnpredictable chronic stress can set appetite, body mass and the rate of gastric emptying, intestinal propulsive function deducing apparently.(P <0.01)There is no significant pathology change in gastrointestinal tissue. The contents of MTL, GAS, Ghrelin in experimental mice serum(P<0.01) and brain, stomach and duodenum Ghrelin and GHSR mRNA lower distinctly(P<0.01). For the indicators of Simo Decoction group and domperidone group,appetite and weight significantly grow(P<0.01). Gastric emptying, intestinal propulsive function can be restored(P<0.05).The contents of MTL, GAS, Ghrelin of serum cause an increase.The two groups exist no statistical significance (P>0.05). In positive expression aspect of Ghrelin and its receptor GHSR mRNA in brain and gastric tissue, Simo Decoction group compared with the model group increased significantly(P<0.01),domperidone group compared with the model group increase (P<0.05). In positive expression aspect of Ghrelin and its receptor GHSR mRNA in duodenum tissue, Two groups group compared with model are elevated (P<0.05), Simo decoction group and domperidone groups exist no statistical significance (P>0.05).Conclusion:1.Simo Decoction can effectively improve symptoms and gastrointestinal-emptying of FD patients.Clinical efficacy of Simo Decoction is equivalent to Domperidone groups.2.The Ghrelin content of plasma in FD patients is apparently reduced and assumes the inverse correlation with the condition order of severity. Simo Decoction can adjust patients’plasma Ghrelin levels, slightly better than Domperidone group.3. FD patients with anxiety, depression significantly higher than the normal people, the extent of dyspepsia symptoms and the grade of SAS and SDS are positively correlated. Simo Decoction reduce the grade of SAS and SDS, improve anxiety condition but there is no improvement for depression situations.4.Simo Decoction not only can promote the rate of gastric emptying in chronic stress of mice and increase appetite,weight for unpredictable chronic stress of mice but also adjust the level of MTL, GAS, Ghrelin of serum and brain, stomach, and small intestine Ghrelin and GHSR mRNA expressions.5. The possibility of the treatment of FD with the mechanism of Simo Decoction could be achieved by adjusting the level of braingut peptide and balance of brain-gut axis.Furthermore,it provide Chinese medicine, liver and spleen related theory of modern biological basis with brain-gut axis imbalances hypothesis.更多还原