| ObjectiveFunctional dyspepsia (FD), a common functional gastrointestinal disease in clinic, is a syndrome represented a group of symptoms caused by duodenum and stomach dysfunction, without organic diseases. Studying the mechanism of Chinese medicine syndromes could help expand Chinese medicine theory, assess the effect of Chinese medicine. In the research, we studied the mechanism of the spleen deficiency syndrome of FD, a core syndrome of this disease TCM, and expanded the theory of TCM.MethodsIn theatrical study, the TCM type of syndromes and its distribution of FD were studied and the high frequency TCM syndromes with symptoms of them were counted. Collection and analysis the items including distension or fullness in TCM ancient books to find the evolution of abdominal distension or fullness, and its pathogenesis based on theatrical study 1. The literature of gastric distension or fullness was also analysised to find the pathway of this sensory production. Then, collected and analysed the Chinese herbs and decoctions of Piman, fullness or distention in TCM ancient book to find the Chinese medicine formula principal of FD.In experimental study, animal model was reconstructed by transient neonatal gastric irritation with iodoacetamide (IA) oral gavages and IA with modified multiple platform method. Appearance, body weight, quantity of food and water in-take, sucrose preference, and gastric hypersensitivity were observed to assess whether it is the model of spleen deficiency syndrome of FD.The animal models were reconstructed followed experimental study 1, and brain-gut peptide (Ghrelin, CCK, VIP, SS, SP, CGRP) in stomach, serum and hypothalamus were tested through immunohistochemistry, Elisa, Real-time PCR.After, reconstruct the animal models of spleen deficiency syndrome of FD, the model rats were treated by XSLJZD, and the domperidone was the control drug. The appearance, quantity of food and water in-take, sucrose preference, and gastric hypersensitivity were observed to assess the effect of XSLJZD.At the mean while, two types of spleen deficiency syndrome of FD models were treated by XSLJZD, with domperidone as the control drug. The brain-gut peptide (Ghrelin, CCK, VIP, SS, SP, CGRP) in stomach, serum, and hypothalamus was detected through immunohistochemistry, Elisa, Real-time PCR.ResultsTheatrical study, in the clinical literatures, the highest frequency of TCM syndromes of FD was as follow:the syndrome of disharmony between the liver and stomach, deficiency of the spleen and stomach, distorted mixtures of cold with heat, food stagnation, the depressed liver with the insufficient spleen, liver stasis, deficiency-cold of the spleen and stomach, and heat and dampness in the spleen and stomach. Among these syndromes, epigastric fullness is the common symptom. This finding helped for the study of the TCM syndrome mechanism.After ancient book study, we found that, in TCM, the distension or fullness was caused by qi-deficiency or stagnation of cold, heat, humidity, phlegm, food and blood in the abdomen. The brain-gut peptide, communicating CNS and ENS, regulated the gastric distension. Diseases represented distension or fullness in TCM were also analysised. In the research, Piman, distension or fullness of TCM, had the same discomfort part and disease progress with FD, which could be considered as the TCM name of FD. The TCM pathogenesis of Piman was spleen deficiency or qi stagnation, appetite was the standard distinguishing deficiency and excess syndrome of TCM. This finding gave the standard for the model of spleen deficiency syndrome of FD and effect of Chinese medicine.We also studied the Chinese medicine formula principal of FD. The Chinese herbs of decoctions of fullness-treating in higest frequency were the main compositions of Xiangsha Liujunzi decotion, which could be the main Chinese medicine treating FD. Chinese herbs treating fullness of regulating qi, tonic, dampness drying, phlegm resolving, in high frequency, combining their flavor and meridian tropism, could modify Xiangsha Liujunzi decotion according to the symptoms of FD.In experimental study, the IA and IA with modified multiple platform method models all had less food and water in-take, low sucrose preference, and gastric hypersensitivity. The rats of IA with modified multiple platform method got lower body weight and more fatigue. Both models met the standards of functional dyspepsia with spleen deficiency, however, IA with modified multiple platform method model appeared more spleen deficiency-like behavioral.About the mechanism, the peptides of Ghrelin, CCK, and VIP in the stomach, serum and hypothalamus of both models were reduced, however, these peptides mRNA in hypothalamus of model rats were increased. The feedback regulation might make this difference. The production of SS and its mRNA in stomach, serum and hypothalamus were increased in both model groups, and the IA model increased more. The SP and CGRP peptides in the stomach of IA with modified multiple platform method model group were more than those of IA model and control groups. CGRP in serum of IA with modified multiple platform method model group was decreased. Others had no significant difference. The decreasing of brain-gut peptides (Ghrelin, CCK, VIP) having the function of increasing appetite and decreasing the tone of stomach wall, and increasing of inhibitory peptide (SS) might the mechanism of spleen deficiency syndrome in TCM of FD. The difference in the expression of SP, CGRP and SS might the mechanism of two types of spleen deficiency syndromes in TCM. The spleen deficiency syndromes with low appetite and body weight represented threshold of pain decreasing, and more gastric hypersensitivity while the other syndrome with low appetite and heavy body weight represented brain-gut peptide disorder.After the treatment, we found that XSLJZD increased the food-intake, SP (sucrose preference) and decreased the gastric hypersensitivity of the models rats with dose-depending. In the research, XSLJZD increased the appetite and food-intake, alleviated fullness of FD with spleen deficiency rats. It also alleviated lusterless fur and fatigue of model rats. XSLJZD had the effect to spleen deficiency syndrome of FD. Our finding also proved the model reconstructed by IA and IA with modified platform method met the standard of spleen deficiency syndrome of FD.About the brain-gut peptide, XSLJZD increased the production of Ghrelin, CCK, and VIP in the stomach and in serum and hypothalamus indirectly. It also decreased the SS of model rats in stomach, serum, and hypothalamus. XSLJZD also decreased the SP in the stomach of model 2, did not change the SP and CGRP in serum and hypothalamus. We found that, XSLJZD alleviated the symptoms of spleen deficiency syndrome of FD by regulating the production brain-gut peptide. This finding proved the mechanism of spleen deficiency with dyspepsia is disorder of brain-gut peptide which expand the theory of spleen deficiency theory in TCM.ConclusionsIn TCM, gastric distension or fullness is the main symptom of FD, and Piman, distension and fullness in TCM could be considered as the Chinese medicine name of FD. The pathogenesis of Piman is in the spleen in TCM, and appetite distinguishes deficiency and excess syndromes. Based on this theory, the model of spleen deficiency syndrome of FD was reconstructed and the mechanism of spleen deficiency was studied. In our study, both the model reconstructed by IA and IA with modified platform method met the standard of spleen deficiency syndromes of FD and co-related with brain-gut peptide which could be alleviated and regulated by spleen strengthen decoction. The disorder of brain-gut peptide might the mechanism of spleen deficiency with dyspepsia, which expanded the theory of spleen deficiency in TCM.
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