| ObjectiveFunctional dyspepsia is a functional gastrointestinal disease with the main clinical manifestations of fullness and discomfort after meals,early discomfort,abdominal parin and burning sensation in the upper abdomen.The prevalence of this disease is high and there is a lack of specific drugs.Although the pathogenesis of functional dyspepsia is unclear,studies have shown that it is closely related to brain-gut peptides.Under the guidance of the syndrome differentiation and the combination of disease and syndrome,traditional Chinese medicine has a good effect on functional dyspepsia.Therefore,this study will explore TCM syndromes of functional dyspepsia(FD)spleen deficiency syndrome,and the biological basis of Xiangsha Liujunzi Decoction intervention in FD spleen deficiency syndrome,aiming to provide a reference for the mechanism of FD and the development of new drugs,and enrich the connotation of syndrome differentiation and Holistic view.MethodsTheoretical research:By searching CNKI.NET and the Ancient Books and the Republic of China Digital Book Platform of Beijing University of Chinese Medicine,we collatied terminology of traditional Chinese medicine related to functional dyspepsia,used comparative analysis to explore the name of traditional Chinese medicine corresponding to functional dyspepsia,a Western medicine disease;meanwhile,to analyze the etiology and pathogenesis of functional dyspepsia.We also applied the method of literature measurement to analyze the main TCM syndrome types of functional dyspepsia;at the same time,under the guidance of the thought of syndrome differentiation and treatment,analyze the theoretical basis of TCM prescription for the treatment of functional dyspepsia syndrome.Literature research:We evaluated the comprehensive efficacy of Xiangsha Liujunzi Decoction in the treatment of functional dyspepsia(symptom improvement,effectiveness,incidence of adverse events,etc.)by systematic review and meta-analysi to provide a basis for clinical application and lay the foundation for the selection of positive drugs and treatment courses in experimental researchExperimental research:First,the model of functional dyspepsia with spleen deficiency syndrome was replicated by standing platform in water with iodoacetamide combined,and the model was evaluated by observing the general condition of rats and gastrointestinal motility.After that,Modified Xiangsha Liujunzi Formula and domperidone were given for drug intervention,and the efficacy of the drug was evaluated by the above indicators,and the counter-proof model was successful.At the same time,we established the method for isolation and culture of gastric antrum smooth muscle cells in rats with functional dyspepsia and spleen deficiency syndrome,and filtered the condition of Xiangsha Liujunzi Decoction drug serum treating smooth muscle cells.On this basis,from the overall level and the level of isolated cells,we moleculared biology experimental techniques were used to detect the brain-gut peptides(SP,SS,Ghrelin,VIP,GAS,CCK,CGRP)in serum,tissue and smooth muscle cells.ResultsTheoretical research:(1)In the theory of Chinese medicine,"fullness","noisy","gastric pain" are closest to functional dyspepsia.The causes of functional dyspepsia include congenital insufficiency,exogenous evil energy,diet,phlegm dampness,qi stagnation,blood stasis,etc.The core pathogenesis is weak spleen,blockage of the middle-focused air machine,and the disease is in the spleen,but with heart,Liver,lung and kidney have a certain relationship.(2)The traditional Chinese medicine syndromes of functional dyspepsia are mainly spleen-qi deficiency syndrome,liver-stomach discordance syndrome,liver-spleen discordance syndrome,spleen-gastric dampness syndrome and cold-heat miscellaneous syndrome,and the proportion of spleen-qi deficiency syndrome is the highest.Under the guidance of the concept of combining traditional Chinese medicine with disease and syndrome,treating spleen deficiency syndrome with functional dyspepsia from the spleen not only meets the pathogenesis characteristics,but also meets the requirements of syndrome differentiation and treatment.Therefore,the treatment of functional dyspepsia with spleen-deficiency syndrome of Xiangsha Liujunzi Jiajian Recipe with the effect of tonifying the spleen and regulating the spleen is theoretically feasible and scientific.Literature Research:A systematic review and meta-analysis of a randomized controlled trial of Xiangsha Liujunzi Decoction in the treatment of functional dyspepsia found that Xiangsha Liujunzi Decoction can improve the symptoms and improve the quality of life of patients with functional dyspepsia,while reducing the recurrence rate and the incidence of adverse events.Regardless of whether Xiangsha Liujunzi Decoction is used alone,or Xiangsha Liujunzi Decoction is used in combination with conventional treatment drugs,the effective rate is significantly higher than conventional treatment.Of the 27 studies included,26 studies compare efficiency.In these 26 studies,regardless of whether the course of treatment was 14 days,28 days,or 30 days,the effectiveness of the intervention group was significantly higher than that of the control group.In addition,16 of these 26 studies used only domperidone as a control drug,and a subgroup analysis was conducted on these 16 studies.The results showed that no matter whether Xiangsha Liujunzi decoction was used alone,or combined with Domperidone,the effective rate is higher than domperidone control group.This provides a reference for the drug selection and treatment course of the experimental study.Experimental Study:(1)Rat model of functional dyspepsia with spleen deficiency syndrome was successfully prepared by standing platform in water combined with iodoacetamide.Compared with the control group,the rats in the model group had loose hair,fatigue,less move,and slowincrease in food intake and water intake.Body weight and decreased gastrointestinal motility of model group were significantly reduced.The pathological results of the stomach showed that there were no pathological changes in the stomach of the two groups of rats.(2)After drug intervention,compared with the model group,the general condition,food intake,water intake,and body weight of the rats in the drug administration group have improved,and gastrointestinal motility has been restored.There were no pathological changes in the department and hypothalamus.(3)Biological basic research on the overall level of rats:Compared with the control group,the content of SP,GAS and Ghrelin in the serum and stomach of the model group were significantly reduced,and the contents of SS,VIP,CCK and CGRP were significantly increased.Compared with the model group,domperidone and medium and high doses of Modified Xiangsha Liujunzi Decoction significantly increased the serum and medium SP,GAS,Ghrelin content of rats,domperidone and middle dose of Modified Xiangsha Liujunzi Decoction significantly reduced The content of SS,VIP and CGRP in the serum of rats,while domperidone also reduced the content of VIP,CCK and CGRP in the stomach of rats.The low-dose Modified Xiangsha Liujunzi Decoction reduced the content of SS,VIP and CCK in the stomach of rats Content,and the middle-dose Modified Xiangsha Liujunzi Decoction reduced the content of CGRP in the rat stomach.Compared with Domperidone group,the SP content in the serum of rats in the low-dose Modified Xiangsha Liujunzi Decoction group was significantly reduced,and the serum CCK and CGRP levels were significantly increased.The VIP content in the rat stomach was significantly higher than that in Domperidone group.Compared with the control group,the expression levels of SP mRNA,GAS mRNA,and Ghrelin mRNA in the stomach and hypothalamus of the model group were significantly reduced,while the expression levels of SS mRNA,VIP mRNA,CCK mRNA,and CGRP mRNA were significantly increased.Compared with the model group,domperidone significantly increased the expression levels of SP mRNA,GAS mRNA,and Ghrelin mRNA in the rat stomach and hypothalamus,and decreased the expression levels of SS mRNA,VIP mRNA,CCK mRNA,and CGRP mRNA in the rat stomach and hypothalamus.Compared with the model group,the middle-dose Modified Xiangsha Liujunzi Decoction significantly up-regulated the expression of SP mRNA in the stomach,up-regulated the expression of GAS mRNA and Ghrelin mRNA in the stomach and hypothalamus,while down-regulated the stomach and hypothalamus.SS mRNA,VIP mRNA,CCK mRNA,CGRP mRNA expression.Compared with Domperidone group,the expression levels of GAS mRNA and Ghrelin mRNA in the stomach and hypothalamus of rats in the low-dose Modified Xiangsha Liujunzi Decoction Group were significantly reduced,while the expression levels of SS mRNA,VIP mRNA,and CCK mRNA were significantly increased.Compared with the control group,the SP,GAS,and Ghrelin protein expressions in the model group's stomach and hypothalamus were significantly reduced,and the SS protein expression was significantly increased.Compared with the model group,domperidone and the middle-dose Modified Xiangsha Liujunzi Decoction significantly increased the SP,GAS,and Ghrelin protein expression levels in the stomach and hypothalamus,while down-regulated the SS protein expression levels in the stomach and hypothalamus.Compared with the domperidone group,the SP protein expression and Ghrelin protein expression in the stomach and hypothalamus of rats in the low-dose Modified Xiangsha Liujunzi Decoction were significantly reduced.(4)Enzymatic digestion method was used to successfully isolate and culture the gastric antrum SMC of rats with functional dyspepsia.It is found that 10%drug serum interfering 24 hours is the best condition for the drug serum to interfere the gastric antrum SMC with the CCK-8 method.Compared with the model group,the positive drug group and the high-dose group of Modified Xiangsha Liujunzi Decoction can significantly promote cell proliferation.(5)Cell-level biological basic research found that compared with the control group,the content of SP,GAS,and Ghrelin in the supernatant of the gastric antrum smooth muscle cells of the model group was significantly reduced,SS content increased significantly.Compared with the model group,the domperidone group,medium and high doses of Modified Xiangsha Liujunzi Decoction increased the SP content,GAS content and Ghrelin content in the gastric antrum smooth muscle cell supernatant,while reduced SS content.Compared with the control group,the SP mRNA content of gastric antrum smooth muscle cells in the model group was significantly decreased,while the SS mRNA content was significantly increased.Compared with the model group,the domperidone group,medium and high dose Modified Xiangsha Liujunzi Decoction increased the SP mRNA expression of gastric antrum smooth muscle cells.Medium does Modified Xiangsha Liujunzi Decoction reduced the expression of SS mRNA in gastric antrum smooth muscle cells.Conclusion(1)According to the main symptoms of functional dyspepsia,it is attributed to the categories of dysphagia,noisy,and stomach pain,but it does not analyze the etiology and pathogenesis of FD.In addition,in the process of reading the literature,the author found that the researchers not only attributed FD to ragged,noisy,and stomach pain,but also attributed it to nausea,anorexia,and so on.It can be seen that Chinese medicine's understanding of FD is not yet clear.Therefore,this study systematically consulted modern literature and reference books,at the same time combed ancient literature,analyzed the definition and clinical manifestations of FD,and found that "fullness","noisy","gastric epigastric pain" in Chinese medicine theory is more correspondingly.FD's main etiology of TCM are due to invasion of external evils,improper diet,emotional distress,and excessive thoughts.The pathogenesis of the disease is weak spleen and blockage of the middle-focused air machine.FD is mainly in the spleen,which has a certain relationship with liver,heart,lung and kidney.In the syndrome differentiation of functional dyspepsia,the syndrome of deficiency of spleen qi ranks first.Modified Xiangsha Liujunzi Decoction is theoretically feasible to treat functional dyspepsia.(2)In clinical practice,Xiangsha Liujunzi Decoction can be used to treat functional dyspepsia,improve symptoms,and improve effectiveness.(3)Rats with functional dyspepsia and spleen deficiency syndrome,the gastrointestinal motility has decreased,and the expressions of SP,GAS,and Ghrelin in the serum,gastric antrum,and hypothalamus of the rats have decreased,while SS,VIP,CCK,and CGRP have increased,indicating that abnormal brain-gut peptide expression may be one of the most important pathogenesis of functional dyspepsia with spleen deficiency syndrome.After the intervention of Modified Xiangsha Liujunzi Decoction,it was found that the symptoms and signs of rats with functional dyspepsia and spleen deficiency syndrome were improved,and the gastric motility was enhanced.The drug serum can promote the proliferation of gastric antrum smooth muscle cells.Modified Xiangsha Liujunzi Decoction can up-regulate the expression of SP,GAS and Ghrelin in rat serum,gastric antrum and hypothalamus,while down-regulate the expression of SS,VIP,CCK and CGRP in rat serum,gastric antrum and hypothalamus,suggesting that regulating of brain-gut peptide abnormalities and restoring gastric motility may be one of the mechanisms of the pharmacodynamic effect of Modified Xiangsha Liujunzi Decoction. |
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