脾虚证胃动力障碍的ICC特征及健脾中药干预研究
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摘要
目的
本研究以胃运动起搏细胞—Cajal间质细胞(Interstitial Cell of Cajal,ICC)为主要切入点,从ICC形态与功能、胃电活动、胃排空活动等不同层次探讨脾虚证胃力动障碍的部分发病机制,并为健脾理气代表方香砂六君子汤治疗本病证提供科学的临床与实验依据。
方法
文献研究
部分回顾了20年来国内外学者对脾虚证胃肠运动障碍的认识,综述了胃肠运动研究方法、Cajal间质细胞与胃肠动力障碍疾病及其中医药防治和脾虚证胃肠运动障碍及调控机制研究现状,展望了未来研究新的方法和方向。
临床研究
对60例西医诊断为慢性胃炎伴有胃肠运动障碍的脾虚证患者用传统的以症状、舌象、脉象进行中医辨证定型,将符合纳入标准的患者随机分为中药治疗组和西药治疗组,另外选择正常人10例作胃排空、胃电图对照组。中药治疗组用香砂六君子汤(组成和用量参照《方剂学》教材):白术15g,甘草10g,制半夏15g,党参15g,陈皮10g,茯苓15g,木香10g(后下),砂仁10g(后下),每日一剂。上方加水500ml,煎取200ml,分早、晚饭前半小时服用,四周为一个疗程。西药用莫沙必利:每次1片(5mg/片),每天3次,三餐前20分钟服用,四周为一个疗程。自观察之日起,要求病人忌烟、酒、茶及辛辣刺激、煎炸油腻等不宜消化的食物,停用任何影响疗效判定的药物。采用症状分级量化法行慢性胃炎消化不良症状、脾虚证候的临床缓解率、总有效率评定。并采用不透X线标记物法(钡条法)测定胃排空率,采用体表记录法记录胃电图(EGG)以观察脾气虚患者治疗前后上述指标的变化。
实验研究
以脾虚证SD大鼠模型为研究对象,应用胃排空检测、普通显微镜、电子显微镜、免疫组织化学、RT-PCR技术等方法,观察脾虚型大鼠模型给予香砂六君子汤干预前后的胃动力变化、胃起搏区ICC的形态特征、数量和ICC细胞标志物c-kit基因表达变化。
所得数据采用单因素方差分析,组间两两比较采用SNK法。分析各指标和证型关系,探讨脾虚证胃肠运动障碍的部分发病机制和健脾理气中药的部分作用机制。
ObjectiveThe research made gastric movement' s pacemaking cell and Interstitial Cell of Cajal (ICC) as the incision, probed into the pathological mechanism of gastric movement obstruction caused by spleen deficiency syndrome from the form and function of ICC, electricgastro- movement, the gastric emptying movement. It also can provide clinical and experimental proof for XiangSha Six Mild-Drug Decoction to treat spleen deficiency syndrome. Method The section of documentary research:Reviewed partly the understanding of domestic and foreign scholars on gastrointestinal movement obstruction caused by spleen deficiency syndrome in the past 20 years, in addition, summarized the study methods of gastrointestinal movement, the relationship of ICC and gastrointestinal movement obstruction disease, TCM therapy on the disease, the status quo of regulating mechanism of gastrointestinal movement obstruction disease, provided future views of the research. Clinical research:selected 60 patients suffered from the spleen deficiency syndrome accompanied gastric movement obstruction, then divided them into different syndrome group according to the TCM' s diagnostic standard composed by
symptoms, tongue condition and pulse condition, etc;divided the cases into Chinese medicine group and Western medicine group, otherwise, took 10 normal persons as control group. In Chinese medicine group, XiangSha Six Mild-Drug Decoction was used: Rhizoma Atractylodis Macrocephalae (Baizhu)15g, Radix Glycyrrhizac (Ganchao)lOg, Rhizoma Pinelliae(Banxia)15g, Radix Codonopsis (Dangshen) 15g, Pericarpium Citri Reticulatae (Chenpi) lOg, Poria(Fuling) 15g, Radix Aucklandiae (Muxiang) lOg (decoct later), Fructus Amomi (Sharen) lOg (decoct later), one dose one day. Used 500ml water, decocting 200ml decoction, the patients had it half an hour before the breakfast and supper, 4 weeks as a period of treatment. In Western medicine group, Mosapride Citrate Tablets was used. One tablet once (5mg/tablet) , 3 times one day, the patients had it 20 minutes before 3 meals, 4 weeks as a period of treatment. From inspecting day, the patients were asked to avoid tobacco, wine, tea and acrid and fried things, stoppped using any medicine which could affect curative effect. Used the method of symptom classification and fix quantity to evaluate the relieving ratio of spleen deficiency syndrome, adopted X-ray prevention marked substances (Barium Slip Method) to measure gastric emptying ratio, adopted body description method to record Electrogastrogram, In the end, observed the change of indexes mentioned above, which was recorded from the patients suffered from spleen deficiency syndrome before and after the treatment. Experimental research:SD model rats suffered from spleen deficiency syndrome were used as objects, adopted gastric emptying detection, electron microscopic, immunity organization chemistry and RT-RCR techniques, etc. Before and after giving XiangSha Six Mild-Drug Decoction to the rats, observed the change of gastric motility. Form and distributing characteristics of ICC gastric pace-maker unit, gene-expressing variety of ICC cell marked substance c~kit.Single factor variance was adopted to analyze the dates. Between the group' s compare, SNK technique was adopted, the research analyzed the relationship between index and syndrome differentiation, discussed the segmental pathological basis of spleen deficiency syndrome that causing gastric movement obstruction and regulating mechanism of Chinese medicine.
Achievement Clinical research:l.The relieving ratio of alimentary tract symptoms of patients suffered from the spleen deficiency syndrome of chronic gastritis.In the relieving ratio of alimentary tract symptoms of the patients, the XiangSha Six Mild-Drug Decoction group was higher than that of Western medicine group, there was obvious difference between them(P<0. 05).2. The gastric emptying ratio of patients suffered from the spleen deficiency syndrome of chronic gastritis.(1) In the gastric emptying ratio before treatment: there was obvious difference between subject group (Chinese medicine group and Western medicine group) and control group (P<0. 01).(2) In the gastric emptying ratio after treatment: there was no obvious difference between subject group (Chinese medicine group and Western medicine group) and control group (P>0. 05), there was obvious difference to the gastric emptying ratio before treatment (P<0.01).3.EGG analysis of patients suffered from the spleen deficiency syndrome of chronic gastritis .(1) In stomach electrical rhythm analysis before the meal:Comparing with control group, the regular slow wave of the Chinese medicine group and Western medicine group reduced obviously (P<0. 01), over-slow rhythm increased obviously (P<0.01), over-fast rhythm has no obvious difference (P>0. 05), Comparing with the control group, regular slow-wave and over-slow rhythm of Chinese medicine group had no obvious difference after treatment (P>0.05), but the Western medicine group still had obvious difference(2) In PDP analysis before and after the meal:Comparing with the control group, the PDP analysis before and after the meal decreased obviously in both Chinese medicine group and Western medicine group(P>0. 05), There was no obvious difference after treatment (P>0. 05).Experimental research:1. In model rats suffered from spleen deficiency syndrome, there was gastric emptying obstruction.
2. In model rats suffered from spleen deficiency syndrome, the proportion of ICC cytoplasm in gastric muscular layer decreased, chondriosome swelled, endoplasmic reticulum dilated.3. In model rats suffered from spleen deficiency syndrome, mRNA and protein expression of c-kit gene in gastric muscular layer decreased .4. The XiangSha Six Mild-Drug Decoction could improve situation above.Conclusion1 There was gastric emptying obstruction in patients suffered from the spleen deficiency syndrome of chronic gastritis.2 In patients suffered from the spleen deficiency syndrome of chronic gastritis, electrogastro- movement decreasing was the mechanism of electrical physiology of gastric emptying obstruction.3 In patients suffered from the spleen deficiency syndrome of chronic gastritis, the XiangSha Six Mild-Drug Decoction could improve dyspepsia symptoms and gastric emptying obstruction, its mechanism had relationship with its improving electrogastro- movement.4 In model rats suffered from spleen deficiency syndrome, there was abnormality in the form and function of ICC in gastric muscular layer, The XiangSha Six Mild-Drug Decoction could improve situation above.
本研究以胃运动起搏细胞—Cajal间质细胞(Interstitial Cell of Cajal,ICC)为主要切入点,从ICC形态与功能、胃电活动、胃排空活动等不同层次探讨脾虚证胃力动障碍的部分发病机制,并为健脾理气代表方香砂六君子汤治疗本病证提供科学的临床与实验依据。
方法
文献研究
部分回顾了20年来国内外学者对脾虚证胃肠运动障碍的认识,综述了胃肠运动研究方法、Cajal间质细胞与胃肠动力障碍疾病及其中医药防治和脾虚证胃肠运动障碍及调控机制研究现状,展望了未来研究新的方法和方向。
临床研究
对60例西医诊断为慢性胃炎伴有胃肠运动障碍的脾虚证患者用传统的以症状、舌象、脉象进行中医辨证定型,将符合纳入标准的患者随机分为中药治疗组和西药治疗组,另外选择正常人10例作胃排空、胃电图对照组。中药治疗组用香砂六君子汤(组成和用量参照《方剂学》教材):白术15g,甘草10g,制半夏15g,党参15g,陈皮10g,茯苓15g,木香10g(后下),砂仁10g(后下),每日一剂。上方加水500ml,煎取200ml,分早、晚饭前半小时服用,四周为一个疗程。西药用莫沙必利:每次1片(5mg/片),每天3次,三餐前20分钟服用,四周为一个疗程。自观察之日起,要求病人忌烟、酒、茶及辛辣刺激、煎炸油腻等不宜消化的食物,停用任何影响疗效判定的药物。采用症状分级量化法行慢性胃炎消化不良症状、脾虚证候的临床缓解率、总有效率评定。并采用不透X线标记物法(钡条法)测定胃排空率,采用体表记录法记录胃电图(EGG)以观察脾气虚患者治疗前后上述指标的变化。
实验研究
以脾虚证SD大鼠模型为研究对象,应用胃排空检测、普通显微镜、电子显微镜、免疫组织化学、RT-PCR技术等方法,观察脾虚型大鼠模型给予香砂六君子汤干预前后的胃动力变化、胃起搏区ICC的形态特征、数量和ICC细胞标志物c-kit基因表达变化。
所得数据采用单因素方差分析,组间两两比较采用SNK法。分析各指标和证型关系,探讨脾虚证胃肠运动障碍的部分发病机制和健脾理气中药的部分作用机制。
ObjectiveThe research made gastric movement' s pacemaking cell and Interstitial Cell of Cajal (ICC) as the incision, probed into the pathological mechanism of gastric movement obstruction caused by spleen deficiency syndrome from the form and function of ICC, electricgastro- movement, the gastric emptying movement. It also can provide clinical and experimental proof for XiangSha Six Mild-Drug Decoction to treat spleen deficiency syndrome. Method The section of documentary research:Reviewed partly the understanding of domestic and foreign scholars on gastrointestinal movement obstruction caused by spleen deficiency syndrome in the past 20 years, in addition, summarized the study methods of gastrointestinal movement, the relationship of ICC and gastrointestinal movement obstruction disease, TCM therapy on the disease, the status quo of regulating mechanism of gastrointestinal movement obstruction disease, provided future views of the research. Clinical research:selected 60 patients suffered from the spleen deficiency syndrome accompanied gastric movement obstruction, then divided them into different syndrome group according to the TCM' s diagnostic standard composed by
symptoms, tongue condition and pulse condition, etc;divided the cases into Chinese medicine group and Western medicine group, otherwise, took 10 normal persons as control group. In Chinese medicine group, XiangSha Six Mild-Drug Decoction was used: Rhizoma Atractylodis Macrocephalae (Baizhu)15g, Radix Glycyrrhizac (Ganchao)lOg, Rhizoma Pinelliae(Banxia)15g, Radix Codonopsis (Dangshen) 15g, Pericarpium Citri Reticulatae (Chenpi) lOg, Poria(Fuling) 15g, Radix Aucklandiae (Muxiang) lOg (decoct later), Fructus Amomi (Sharen) lOg (decoct later), one dose one day. Used 500ml water, decocting 200ml decoction, the patients had it half an hour before the breakfast and supper, 4 weeks as a period of treatment. In Western medicine group, Mosapride Citrate Tablets was used. One tablet once (5mg/tablet) , 3 times one day, the patients had it 20 minutes before 3 meals, 4 weeks as a period of treatment. From inspecting day, the patients were asked to avoid tobacco, wine, tea and acrid and fried things, stoppped using any medicine which could affect curative effect. Used the method of symptom classification and fix quantity to evaluate the relieving ratio of spleen deficiency syndrome, adopted X-ray prevention marked substances (Barium Slip Method) to measure gastric emptying ratio, adopted body description method to record Electrogastrogram, In the end, observed the change of indexes mentioned above, which was recorded from the patients suffered from spleen deficiency syndrome before and after the treatment. Experimental research:SD model rats suffered from spleen deficiency syndrome were used as objects, adopted gastric emptying detection, electron microscopic, immunity organization chemistry and RT-RCR techniques, etc. Before and after giving XiangSha Six Mild-Drug Decoction to the rats, observed the change of gastric motility. Form and distributing characteristics of ICC gastric pace-maker unit, gene-expressing variety of ICC cell marked substance c~kit.Single factor variance was adopted to analyze the dates. Between the group' s compare, SNK technique was adopted, the research analyzed the relationship between index and syndrome differentiation, discussed the segmental pathological basis of spleen deficiency syndrome that causing gastric movement obstruction and regulating mechanism of Chinese medicine.
Achievement Clinical research:l.The relieving ratio of alimentary tract symptoms of patients suffered from the spleen deficiency syndrome of chronic gastritis.In the relieving ratio of alimentary tract symptoms of the patients, the XiangSha Six Mild-Drug Decoction group was higher than that of Western medicine group, there was obvious difference between them(P<0. 05).2. The gastric emptying ratio of patients suffered from the spleen deficiency syndrome of chronic gastritis.(1) In the gastric emptying ratio before treatment: there was obvious difference between subject group (Chinese medicine group and Western medicine group) and control group (P<0. 01).(2) In the gastric emptying ratio after treatment: there was no obvious difference between subject group (Chinese medicine group and Western medicine group) and control group (P>0. 05), there was obvious difference to the gastric emptying ratio before treatment (P<0.01).3.EGG analysis of patients suffered from the spleen deficiency syndrome of chronic gastritis .(1) In stomach electrical rhythm analysis before the meal:Comparing with control group, the regular slow wave of the Chinese medicine group and Western medicine group reduced obviously (P<0. 01), over-slow rhythm increased obviously (P<0.01), over-fast rhythm has no obvious difference (P>0. 05), Comparing with the control group, regular slow-wave and over-slow rhythm of Chinese medicine group had no obvious difference after treatment (P>0.05), but the Western medicine group still had obvious difference(2) In PDP analysis before and after the meal:Comparing with the control group, the PDP analysis before and after the meal decreased obviously in both Chinese medicine group and Western medicine group(P>0. 05), There was no obvious difference after treatment (P>0. 05).Experimental research:1. In model rats suffered from spleen deficiency syndrome, there was gastric emptying obstruction.
2. In model rats suffered from spleen deficiency syndrome, the proportion of ICC cytoplasm in gastric muscular layer decreased, chondriosome swelled, endoplasmic reticulum dilated.3. In model rats suffered from spleen deficiency syndrome, mRNA and protein expression of c-kit gene in gastric muscular layer decreased .4. The XiangSha Six Mild-Drug Decoction could improve situation above.Conclusion1 There was gastric emptying obstruction in patients suffered from the spleen deficiency syndrome of chronic gastritis.2 In patients suffered from the spleen deficiency syndrome of chronic gastritis, electrogastro- movement decreasing was the mechanism of electrical physiology of gastric emptying obstruction.3 In patients suffered from the spleen deficiency syndrome of chronic gastritis, the XiangSha Six Mild-Drug Decoction could improve dyspepsia symptoms and gastric emptying obstruction, its mechanism had relationship with its improving electrogastro- movement.4 In model rats suffered from spleen deficiency syndrome, there was abnormality in the form and function of ICC in gastric muscular layer, The XiangSha Six Mild-Drug Decoction could improve situation above.
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