基于脾藏神理论探讨脾虚胃溃疡大鼠脑肠肽的变化机制

发布时间：2018-02-27 16:43

本文关键词： 脾胃神志胃溃疡血管活性肠肽生长抑素　出处：《北京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:五脏藏神理论是《黄帝内经》脏象学说的重要部分,脾胃为五脏之枢,在五脏整体协调神志中,起着关键作用。本课题旨在通过理论和实验研究,对脾胃病理状态下与精神情志之间的相互关系和作用机制进行探讨,以期揭示脾胃对神志活动的调节作用,为脾藏神理论提供实验依据。方法:本课题实验研究以Wistar大鼠为研究对象,分为正常组、模型组、四君子汤组(造模加灌胃四君子汤)、雷尼替丁组(造模加灌胃雷尼替丁)。采用苦寒泻下、饥饱失常加食醋灌胃相结合的方法,复制脾虚胃溃疡动物模型。观察大鼠的体重、外观、精神活动,饮食排便等体征表现,并进行HE常规染色检测。采用免疫组化法检测胃组织中MTL、VIP、SS、EGF的表达变化,采用酶联免疫(ELISA)法检测血清中VIP、SS的表达变化。结果:1.一般情况:正常组大鼠整体状况良好,二便、饮食、活动正常;模型组大鼠便溏、消瘦、精神萎靡、喜扎堆、毛色不荣,脾虚症状明显;四君子汤组大鼠体重不及正常组,其他脾虚症状均有改善,精神、活动等正常;雷尼替丁组大鼠症状体征与模型组相近。2.光镜下HE染色观察大鼠胃组织病理切片,模型组大鼠胃黏膜损伤明显,黏膜上皮消失,基底层暴露,有血液渗出。正常组和四君子汤组胃组织形态结构大体正常;雷尼替丁组黏膜下层细胞有炎性渗出。3.免疫组化法观察大鼠胃黏膜MTL、VIP、SS、EGF的表达,模型组MTL、VIP、SS、EGF较正常组明显降低,差异有统计学意义(P0.05);四君子汤组、雷尼替丁组MTL、VIP、SS、EGF表达较模型组有升高趋势,差异有统计学意义(P0.05)。4.ELISA检测大鼠血清内VIP、SS的含量,模型组VIP、SS较正常组明显降低,差异有统计学意义(P0.05);四君子汤组、雷尼替丁组VIP、SS表达较模型组升高,差异有统计学意义(P0.05)。结论:1.胃溃疡患者往往存在焦虑、抑郁等精神情志障碍,精神情志异常在胃溃疡的发生和发展中具有重要意义。胃溃疡与精神情志相互影响,是中医"脾藏神"理论的重要体现。2.在研究中,我们采用苦寒泻下加食醋灌胃并配合饥饱失常法,复制脾虚胃溃疡病证结合动物模型。模型大鼠除出现饮食减少,体重增加缓慢甚至降低,稀便或黏液便,肛周毛色污秽,懒动扎堆,眯眼,乏力,耳尖色淡,背毛松散,毛色不荣等脾虚表现,亦见胃黏膜病理损害,HE染色光镜下观察,可见损伤深至黏膜肌层,因此判定模型复制成功。3.脑肠相关神经肽是在中枢系统和胃肠系统中均有分布的活性物质,具有胃肠激素和神经递质的双重作用。本次试验研究脾虚胃溃疡大鼠胃黏膜和血清脑肠肽分泌异常。推测胃溃疡患者存在脑肠神经肽分泌失常,脑-肠轴调节紊乱,可能是胃溃疡患者伴随精神情志障碍的主要机制。4.四君子汤干预治疗作用,能够有效改善大鼠脾虚症状,预防胃溃疡的发生,同时对脾虚胃溃疡大鼠胃黏膜和血清中脑肠肽的表达也有明显的改善作用。提示益气健脾(四君子汤)改善脾胃功能,运化气血,调理气机,可能是是通过脑-肠轴调节脑肠肽的分泌,纠正异常表达的脑肠肽,从而发挥调节神志的作用。
[Abstract]:Objective: the five internal organs theory of God is < Neijing > dirty an important part as the theory of the spleen and stomach to 5 of the pivot, in five overall coordination consciousness, plays a key role. The aims of the theoretical and experimental research to explore the relationship and mechanism between the spleen and stomach and pathological state of the mind and spirit. In order to reveal the role of the spleen and stomach of mental activities, to provide the experimental basis for the spleen theory of God. Methods: this project research in Wistar rats as the research object, divided into normal group, model group, Sijunzi Decoction group (four rats with gastric perfusion of Four Gentlemen Decoction), ranitidine group (model + irrigation ranitidine). The stomach cold diarrhea, method of hunger and vinegar lavage combined model, spleen deficiency gastric ulcer rats. Animal weight, appearance, mental activity, diet, defecation symptoms, routine HE staining and immunohistochemical group. The detection method of gastric tissue in MTL, VIP, SS, EGF expression changes, using enzyme-linked immunosorbent assay (ELISA) method for detection of serum VIP, the expression of SS. Results: 1. general condition: the overall situation of the rats in the normal group, two, diet, normal activities; loose stools, the rats in the model group. Thin, apathetic, like to get together, the hair color is not glory, spleen deficiency symptoms; weight four Sijunzi Decoction group rats than in normal group, spleen deficiency and other symptoms were improved, mental activities, normal; ranitidine group rats signs and symptoms similar to model group to observe the pathological sections of gastric tissue of rats with.2. HE staining under light microscope. The model of gastric mucosal injury in rats were obvious, the mucosal epithelium disappeared, basal layer exposed, with oozing of blood. Four normal group and Sijunzi Decoction group stomach morphology in normal group; submucosal cells and inflammatory exudation of ranitidine.3. immunohistochemical method to observe the gastric mucosa of MTL rats, VIP, SS, EGF expression, The model group MTL, VIP, SS, EGF significantly decreased compared with normal group, the difference was statistically significant (P0.05); four Sijunzi Decoction group, ranitidine group MTL, VIP, SS, EGF expression increased compared with the model group, the difference was statistically significant (P0.05).4.ELISA rats were detected in serum VIP, SS content the VIP model group, SS significantly decreased compared with normal group, the difference was statistically significant (P0.05); four Sijunzi Decoction group, ranitidine group VIP, the expression of SS was higher than that in model group, the difference was statistically significant (P0.05). Conclusion: 1. gastric ulcer patients often suffer from anxiety, depression and other mental disorders, mental abnormalities is important the significance in the occurrence and development of gastric ulcer. Gastric ulcer and emotional interaction, is the Chinese medicine "the spleen God" theory an important manifestation of.2. in the study, we use cold diarrhea with vinegar and gavage with irregular diet, spleen deficiency gastric ulcer disease combined with syndrome animal model. The rats in the diet decreased, body weight increased slowly and even lower stools or mucus, perianal fur dirty, lazy get together, squinting, fatigue, ear apex pale, back hair loose and hair color glory with performance, see also the pathological damage of gastric mucosa, observe HE staining under light microscope visible damage, deep to the muscularis mucosa, therefore determine the model successfully reproduced.3. brain gut related neuropeptides are in the central nervous system and gastrointestinal system in both the distribution of active substances, with the dual role of gastrointestinal hormones and neurotransmitters. The abnormal secretion of this experimental study of spleen deficiency gastric mucosa of rats with gastric ulcer and serum ghrelin. That stomach ulcer patients have brain neuropeptides secretion disorders, brain gut axis adjustment disorder, may be the main mechanism of therapeutic effect of gastric ulcer in patients with mental disorders.4. Four Gentlemen Decoction intervention can effectively improve the symptoms of spleen deficiency rats, prevent occurrence of gastric ulcer, At the same time on the expression of spleen deficiency gastric mucosa of rats with gastric ulcer and serum brain gut peptide plays a significant role in improving the prompt. Qi and spleen (Four Gentlemen Decoction) to improve the function of the spleen and stomach, and blood transport, air conditioning machine, may be the secretion and regulation of brain gut peptide by brain gut axis, correct the abnormal expression of brain gut peptide as, to regulate the function of mental function.

【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R22

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