| Gastric cancer is common malignant tumor in China, the incidence of gastric cancer is a multi-factor, multi-stage process, from normal gastric mucosa to gastric carcinoma to undergo a long process of evolution.This is pathology change from normal gastric mucosa to CSG, atrophic gastritis,intestinal metaplasia ,dysplasia ,gastric cancer.Chronic atrophic gastritis is a clinical common diseases. The pathology of Chronic atrophic gastritis is often accompanied by intestinal metaplasia and dysplasia, particularly associated with atypical hyperplasia have a higher malignant transformation rate, which is closely related with gastric cancer, is called as precancerous lesions. Precancerous lesions of gastric carcinoma exist abnormal proliferation of gastric epithelial cells and apoptosis. There is the imbalance between cell proliferation and apoptosis. As the severity of gastric mucosal lesions, apoptosis increasing and proliferation reducing that increase opportunity for malignant transformation of gastric mucosal cells. Apoptosis reducing is the main reasons for gastric mucosal dysplasia. In treatment, the efficacy of Western medicine is not very satisfactory, the current many researches of Chinese medicines have been done. Chronic atrophic gastritis with dysplasia was called as "stomachache" in Chinese medicine and this discase may undergo relatively long duration, so that qi disorder can affect blood active, cause disharmony between qi and blood. Blood stasis has always been through the disease. Most scholars believe that the spleen deficiency and blood stasis are the basic pathogenesis, Invigorating spleen and removing stasis treatment can affect the gastric mucosal cell proliferation and apoptosis levels.Mitochondrial control of cell life activities center as well as the regulation of apoptosis, many of the factors activate the apoptosis pathway through the mitochondrial. Present studying apoptosis mechanisms in precancerous lesions gastric from the mitochondrial pathway of is fewer. Our studying base on pathogenesis of precancerous lesions of gastric carcinoma. Through the indicators adopted ,we detect to study the Invigorating spleen, removing stasis, Invigorating spleen and removing stasis Herbs on the efficacy of gastric precancerous lesions of the similarities and differences from mitochondrial pathway, to infer different characteristics of Chinese medicine prescriptions, and effect of them to apoptosis, to provide ideas for the prevention and treatment of gastric cancer.Purpose:1 Through the analysis pathogenesis of chronic atrophic gastritis with dysplasia, to explore relation between precancerous lesions of gastric carcinoma and apoptosis.2 To set up rats model of chronic atrophic gastritis with dysplasia by exogenous chemical stimuli and eating disorders, to discuss this disease processes and pathogenesis3 Through the application of Invigorating spleen, removing stasis, Invigorating spleen and removing stasis three different traditional Chinese medicine and western medicine, to observe them the different action for apoptosis of gastric precancerous lesions rat from the mitochondrial pathway.Materials and methods:1 Animals and modeling: experimental animal used an ordinary class health wister rats 120, male and female in half, weighing 160±5g, were randomly divided into 11 groups, respectively, including the prevention group and treatment group of Chinese medicine group and western medicine group, modeling group and normal group . Chronic atrophic gastritis with dysplasia rats model were comprehensive set up With irregular diet, feeding with sodium salicylate, hot salt water, drinking sodium deoxycholate.To prevent and treat gastric precancerous lesions by using the Invigorating spleen, removing stasis, Invigorating spleen and removing stasis drugs 2 Chinese medicine prescription consists of Invigorating Spleen medicine , removing stasis medicine and Invigorating spleen and removing stasis Chinese drugs. Invigorating Spleen medicine includes Codonopsis pilosula 15g, Atractylodes 15g and Radix Astragali 15g; Removing stasis Chinese Herbal Medicine includes Salvia miltiorrhiza 15g , panax notoginseng 3g and zedoary turmeric 15g; Invigorating spleen and removing stasis Chinese drugs includes Codonopsis pilosula 15g, Atractylodes 15g, Radix Astragali 15g , Salvia miltiorrhiza 15g, panax notoginseng 3g and zedoary turmeric 15g .These Chinese drugs were purchased from Traditional Chinese Medicine University Hospital pharmacy. According to granule preparation ,we boiled to extract each liquid twice, to adjust the liquid concentration that the doses of Invigorating spleen and removing stasis Chinese drugs group was 1g /ml , the doses of Invigorating spleen group and removing stasis was 0.5g/ml. The Liaoning College of Medicine preparation room provided these drugs. Victoria enzyme was made 0.1g/ml the suspension liquid in distilled water.Reagent: rabbit anti-human P53 monoclonal antibody and secondary antibody were purchased from Dr. Wu Han limited liability company microorganisms. Rhodamine 123, CytochromeC kit antibody, goat anti-mouse IgG (H + L) secondary antibody, Caspase-9 Activity Assay Kit were purchased from biotechnology companies. 3 Samples: a part of samples in gastric antrum tissues were placed in 10% paraformaldehyde solution, fixed, and the other part of samples were place in -70℃refrigerator, a part of sammples were made a single cell suspension liquid immediately.4 Pathological specimens were embedded in paraffin, and sliced, HE stained. Gastric epithelial cell's mitochondrial membrane potential changes and cytochrome C were detected by flowcytometry. P53 protein expression in gastric mucosa were determined with western blotting, Caspase-9 activity of gastric mucosal epithelial cells of precancerous lesions gastric were detected by chemical colorimetric . Result:1 The results of the first part of the thesis are as follow: the normal group rats body, eating were as usual, and rats were good health and weight of their increased natural; model rats appeared downcast , weight loss, lazy activity, apocleisis.The prevention and treatment each group of Chinese and Western medicines was better than the model group in the symptoms. Preventive treatment group pathological picture showed that the incidence of dysplasia in the model was 100%, and mainly concentrated in the moderate and severe dysplasia, 4 cases of moderate and 6 cases of severe, no normal gastric mucosa and light dysplasia ; The cases of Invigorating spleen medicine group in the normal gastric mucosa,Light, moderate and severe dysplasia were the 2 cases, 4 cases, 1 case and 0 case; Removing stasis Chinese drugs group were 3 cases, 3 cases, 3 cases, 0 case; Invigorating spleen and removing stasis Chinese Herbal Medicine Group were 7 cases, 1 case, 0 case, 0 case; Western medicine group were 3 cases, 3 cases, 2 cases, 0 case; The incidence of atypical hyperplasia of Invigorating spleen Medicines group ,removing stasis Chinese Herbal Medicine Group, Invigorating spleen and removing blood stasis group and western medicine group, were respectively (71.4%, 66.6%, 12.5%, 62.5%), and mainly concentrated in the light dysplasia, no severe dysplasia . Invigorating Spleen prevention group, Removing stasis prevention group, Invigorating spleen and removing stasis prevention group, Western prevention group the incidence of light dysplasia were (80%, 50%, 100%, 60%). Chinese drugs ,Western medicine prevention group were lower than model group in the incidence of dysplasia (P<0.05); Therapy group pathological picture showed that model control group concentrated mostly in the moderate and severe dysplasia, 2 cases were moderate and 6 cases were severe, the incidence rate of dysplasia was 100 %, non-normal gastric mucosa and light dysplasia. The cases of Invigorating spleen medicine group in the normal gastric mucosa, Light, moderate and severe dysplasia were 1 case, 5 cases, 3 case s and 0 case; Removing stasis Chinese drugs group were 1 case, 5cases, 4 cases and 0 case; Invigorating spleen and removing blood stasis group were 6 cases, 2 cases, 0 case and 0 case; Western medicine group were 2 cases, 3 cases, 3 cases and 0 case.. Atypical hyperplasia incidence of Invigorating spleen Chinese Medicines, Removing stasis Chinese Herbal Medicine group, Invigorating spleen and removing blood stasis group, and western medicine group was respectively (88.9%, 90%, 25%, 75%). Atypical hyperplasia concentrated mainly in the light dysplasia, the incidence rate of light dysplasia was respectively (62.5%, 55.6%, 100%, 50%) . Chinese drugs ,Western medicine treatment group were lower than model control group in the incidence of dysplasia (P<0.05);2 The results of the second part of the thesis are as follow: showing of rats gastric mucosal cells in P53, In the prevention group, expression of model group P53 was highter than the normal group (P<0.01), Invigorating spleen Chinese drugs group, removing stasis Chinese drugs group , Invigorating spleen and removing stasis Chinese medicine group and Western medicine group was lower than model group in P53 expression (P<0.01), Traditional Chinese medicine were lower than western medicine significantly (P<0.01), Invigorating spleen and removing stasis Chinese medicine was lower than Invigorating spleen Chinese drugs , removing stasis Chinese drugs significantly (P<0.05 or P<0.01 ). In treatment group, the expression of the P53 of model control group was hight than the normal group (P<0.01), three groups of Chinese medicine and Western medicine were lower than model group in P53 expression (P<0.01). Invigorating Spleen and removing stasis Chinese drugs was lower than Invigorating Spleen Chinese medicine, removing stasis Chinese Herbal Medicine and Western medicine significantly (P <0.01). The role of Invigorating Spleen group was similar removing stasis group (P>0.05).3 The results of the third part of the thesis are as follow. Rat gastric mucosal cell mitochondrial membrane potential and cytochrome C determination of the situation are as follow. For the membrane potential (△Ψm), Mitochondrial membrane potential of the model, modeling the control group were hight than the normal group (P<0.05) in prevention group and treatment group. Invigorating spleen, removing stasis group, Invigorating spleen and removing stasis group ,and western medicine group were lower than model group significantly (P<0.05) in prevention and treatment group ,but highter than normal group (P< 0.05). Invigorating spleen and removing stasis group was lower than Invigorating spleen group, removing stasis group and western medicine group significantly (P <0.05). The role of Invigorating spleen group was similar to removing stasis group (P>0.05),.Invigorating spleen group, removing stasis group were similar to western medicine group (P>0.05) .For cytochrome C, in the model, modeling control group was significantly lower than the normal group (P<0.05). cytochrome C of the Invigorating spleen, removing stasis, Invigorating spleen and removing stasis and western medicine group was significantly higher than cytochrome C of the model, modeling control group (P<0.05) in prevention group and treatment group. Invigorating spleen and removing stasis group was significantly highter than Invigorating spleen group, removing stasis group and western medicine group (P<0.05).The role of Invigorating spleen group was similar to removing stasis group (P>0.05) . Invigorating spleen group, removing stasis group was similar to western medicine group (P>0.05).4 The results of the fourth part of the thesis are as follow: Determination of rats gastric mucosal cell caspase9 situation in the model, modeling control group was significantly lower than the normal group (P < 0.05). Through prevention or treatment of drug medication, Invigorating spleen, removing stasis group, Invigorating spleen and removing stasis group,and western medicine group was significantly higher than the model, modeling control group (P<0.05), but lower than normal group (P<0.05). Invigorating spleen group and removing stasis group was significantly highter than Invigorating spleen group, removing stasis group and western medicine group (P<0.05). Invigorating spleen was similar to removing stasis group .And Invigorating spleen groups, removing stasis group was silimar to western medicine group (P>0.05). Conclusions:1 Gastric precancerous lesions exist imbalance between apoptosis and cell proliferation2 With increasing P53 expression of Gastric precancerous lesions ,apoptosis decreased.3 With reduction of mitochondrial transmembrane potential degression of gastric epithelial cells in precancerous lesions , and reduction of release of cytochrome C, apoptosis reduced4 With decreasing caspase-9 activity of gastric epithelial cell precancerous lesions , apoptosis reduced.5 Invigorating spleen group, removing stasis group , Invigorating spleen and removing stasis group Chinese drugs can inhibit and reduce the expression of P53 of gastric precancerous lesions .6 Invigorating spleen, removing stasis, Invigorating spleen and removing stasis Chinese Herbal Medicine can regulate apoptosis through the decreasing mitochondrial membrane potential, increasing the release of cytochrome C of gastric mucosal epithelial cells of gastric precancerous lesions.7 Invigorating spleen, removing stasis, Invigorating spleen and removing stasis Chinese Herbal Medicine can induced apoptosis of gastric mucosal epithelial cells of gastric precancerous lesions. by promoting and raising the expression of caspase-9 activity8 Invigorating spleen, removing stasis, Invigorating spleen and removing stasis Chinese Herbal Medicine spleen can prevent and reverse the gastric epithelial dysplasia .9 Invigorating spleen and removing stasis Chinese Herbal Medicine was more significant than Invigorating spleen Chinese medicine , and removing stasis Chinese Herbal Medicine; Invigorating spleen medicine and removing stasis Chinese Herbal Medicine had similar effects.10 At the molecular level, provided the feasibility of the basis of Invigorating spleen and removing stasis Chinese Herbal Medicine effective treatment for precancerous lesions of gastric carcinoma...
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