| Gastric ulcer have become an ordinary and more disease of digestive system in current clinical, which threaten human's healthy now, there are more 10% people suffer from it in certain period of his life, especially the deficiency cold of spleen and stomach type. Now besides ordinary treatment, drugs treatment play important roles in clinic and oral administration pharmaceutical is still the first chooser. Chinese medicine is suitable for long-term administration and has the character of nimbleness and fewer side-effects and has attained the goal of better cure. The purpose of this experiment is to investigate the anti-ulcer effects and the possible mechanism of WWY.WWY is a Chinese traditional medical prescription derived from the well known"Huangqi Jianzhong decoction"and"Shixiao powder". It could warm the spleen, safeguard stomach against damages. WWY has been widely used in the clinical treatment of gastric ulcer, and achieved excellent effect. The symptoms of gastric ulcer combined with deficiency cold of spleen and stomach type patient treated with WWY, the clinical symptoms were ameliorated remarkably. The purpose of this study is to analyze the mechanism of WWY from the endocrine level of view and explore the significance of inflammatory cytokines in the pathogenesis of gastric ulcer.It was proved that animals experienced many changes in neuroendocrine-immuno systems during gastric ulcer,and these three systems can regulate their functions by endocrinal paracrinal and autocrinal mechanism each other, which suggested that there existed a neuroendocrine-immuno network disease-regulation mechanism during illness such as gastric ulcer. A series of research and observation work for the neuroendocrinal hormones and neuropeptide interrelated to gastrointestinal digestion and absorption demonstrated that functions of neuroendocrine changed and function of gastrointestinal digestion and absorption was obstructed during deficiency cold of spleen and stomach type. However, the research about the mechanism by endocrine system during deficiency cold of spleen and stomach type process is still unclear. And there is little research work for experimental model of deficiency cold of spleen and stomach type combined with gastric ulcer.To explore the regulation of neuroendocrine-immuno network in experimental deficiency cold of spleen and stomach type and deficiency cold of spleen and stomach type combined with gastric ulcer, the present work chose the typical ulcer model of 9 days and mostly healing ulcer model of 52 days after operation, used techniques of ELISA,HE, and studied the changes of GAS,MTL,SS,PGE2 during deficiency cold of spleen and stomach type combined with gastric ulcer process in order to explore the regulation mechanism of endocrine system during deficiency cold of spleen and stomach type combined with gastric ulcer.In this study, healthy male and female Wistar mice were used as experimental animals and randomly divided into five groups, including healthy control group, disease model group, WWY large dose group, and small dose group, Ranitidine Hydrochloride Capsules group. All the mice except healthy control group were used to establish the model deficiency cold of spleen and stomach type combined with gastric ulcer by douche with Dahuang and Okabe. During this process, to judge the state of the mice, we tested the body weight regularly and used cold water to monitor the movement. After 7 days, all the model mice were found to have obvious symptoms, such as low appetite and significant loss of body weight. The result of cold water and let the stomach empty experiment were also less than the mice in healthy control group. These results demonstrated that the model mice had been established successfully. The symptom of each mouse is similar and all the mice could be used for the subsequent experiments.At the 10th day after the beginning of establishing the deficiency cold of spleen and stomach type combined with gastric ulcer model, the model mice were treated with indicated agents through intragastric administration for another 42 days, 2 ml per mice, two times a day. The dose of Ranitidine was determined in accordance with the clinical project. The WWY solution was boiled and evaporated to high concentration for the large dose group, or diluted with PBS for the small dose group based on the formula of dose equivalent conversion ratio by the body surface area between animals and humans. In this process, the body weight was tested regularly. At the 52th day, the mice were sacrificed .Then the blood was collected for the isolation of serum and the serum was stored at low temperature until use. The gastric tissue was also isolated from the mice, embedded, fixed and stored at low temperature until use.We mensurated the GAS,MTL,SS and PGE2 with the method of radiation-immunity technology of wistar rats. The data was analyzed with SPSS soft ware and the result was obtained: SS,MTL and PGE2 in model group were effectively lower than those in normal group (P<0.05) and GAS was higher (P<0.05). All the rats were administrated for 42 days and the indexes in each group rose or fell, especially in normal-dose-Wwy-administrated group and large-dose-Wwy-administrated group. The result suggests that the rats suffered from the deficiency cold of spleen and stomach type combined with gastric ulcer have the disturbance of the incretion level: Ranitidine and WWY, especially WWY can modulate the disturbance. Gastrointestinal gut is a large and complicated endocrinal organ and it release gastrointestinal hormone which can not only modulate the movement of stomach and intestine but can also do it by releasing neurotransmitter. GAS can stimulate the exocrine of gastric acid, pepsin, pamcreatin, promote the contract of gastric antrum, and increase the blood fluid of gastric mucosa. It can also promote the cleavage and proliferation of the gastrointestinal cells, increase the synthesis of DNA and RNA, and expedite the regenerate of gastrointestinal mucosa. Growth hormone release inhibiting hormone is a kind of gastrointestinal hormone with great biological activity and has an effectiveness of suppress. It can reduce the secretion of gastric acid, pepsin, pamcreatin and suppress the exhaustion of stomach and the peristalsis of intestine. It can also suppress the absorption of the intestine and the secretion of gastrin. In our study, the model rats have the disturbance of the proportion between GAS and SS and this suggests the disturbance is one of the etiological mechanisms. WWY can modulate the disturbance and lower the level of GAS and heighten the level of SS,PGE2 and MTL play important roles in the modulation of gastrointestinal physical activities. PGE2 can protect the gastric mucosa and can suppress the secretion of gastric acid, pepsin, stimulate the secretion of mucus and bicarbonate, promote the blood fluid and the regeneration of mucosa. MTL distributes all around the body and have an intensive effectiveness of stimulating the mechanical and electric movement so that it can induce the intensive contraction of the stomach and the evident segmental movement of the intestine. It can also promote the movement of ileum and colon, increase the pressure of stomach and pylorus, and can cleaning the gastrointestinal gut. Our experiments proved that WWY can promote the level of MTL and PGE2.In summary, this study analyzed the underlying mechanism of WWY on the treatment of deficiency cold of spleen and stomach type combined with gastric ulcer from the incretion level of view. The curative effect of WWY attributes to the decreasing of inflammatory cytokines level to some extent, suggesting WWY improved the symptoms of deficiency cold of spleen and stomach type combined with gastric ulcer model mice and treated patients with this type through regulating the incretion level and suppressing the secretion and activity, such as GAS,MTL,SS,PGE2. In addition,this study supported the"NEI", revealing the rationality of traditional Chinese sort combined with modern disease model. This study not only provided valuable experimental data for the treatment of deficiency cold of spleen and stomach type combined with gastric ulcer with traditional Chinese medicine, but also introduced a new direction for the research and development of novel traditional Chinese medicine on gastric ulcer.
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