Different Groups Of Traditional Chinese Medicine The Rat Model Of Gastric Precancerous Lesions In Gastric Mucosa Of Apoptosis

Chronic atrophic gastritis is a common disease of digestive system caused by multiple factors, especially Antral atrophic gastritis and Gastric Cancer have a very close relationship[1,2], therefore it is called Gastric Precancerous conditions diseases. Gastric precancerous lesions is a pathological concept,refers to the gastric epithelial dysplasia (dysplasia, intraepithelial neoplasia). Dysplasia is divided into two levels: mild (low level) and severe (high level), dysplasia (intraepithelial neoplasia) is an important Gastric precancerous lesions. China Consensus of Chronic Gastritis in 2006 indicate that Small Intestinal metaplasia types and complete intestinal metaplasia subtypes have no obvious significance of precancerous lesions. Clinical practice shows that just from the pathological subtypes of intestinal metaplasia we are difficult to predict cancer risk. And in more than a decade, reports of Gastric cancer developed from the Large Intestinal metaplasia types are rare.So the real characteristic pathological changes is dysplasia (or intraepithelial neoplasia). In short, Research on chronic atrophic gastritis with dysplasia has a greater significance for the secondary prevention of gastric cancer.Objective: Treatment of chronic atrophic gastritis with dysplasia by traditional Chinese medicine have a relatively good efficacy. And many studies have shown that the main TCM syndromes of Chronic atrophic gastritis with dysplasia are spleen-deficiency syndrome and blood-stasis syndrome. We use the method of hot salt water combined chemical substances to stimulate the rat model of chronic atrophic gastritis with dysplasia,use Traditional Chinese medicine (YiqiHuayu drugs groups,JianpiYiqi drugs groups and HuoxueHuayu drugs groups )and western medicine(Vitacoenzyme groups) for prevention and treatment. All these measures were hoped to explore effects of different traditional Chinese herbs on gastritic morphological and histological changes in rats with chronic atrophic gastritis with dysplasia, and explore the TCM mechanism of different traditional Chinese herbs and the relationships among different herbs. Materials and methods:1.Take the method that using chemical substances to stimulate animal to replicate the animal models with precancerous lesions of chronic atrophic gastritis and divide them into different groups to therapy. 120 cases of healthy Wisterrats of Ordinary Level with body weight: 160±5 g (60 males and 60 females) were randomly divided into 11 groups,include the normal group, the model group, the Yiqi herbs Prevention group,the Huayu herbs Prevention group,the JianpiHuayu herbs Prevention group, the Western medicine group, the blank group of models,the Yiqi herbs Treatment group, the Huayu herbs Treatment group, the JianpiHuayu herbs Treatment group,the Western medicine Treatment group. Each group has 11 rats except the normal group with 10 rats.Gavage the rats 10ml?kg -1?d -1 hot-salt water (150g/L,55℃) and salicylic acid solution(2%) once a day. Provide 20mmol/l sodium deoxycholate for rats to drink freely. Feed them with the method of saturating 2 days and the turn to fasting 1 day. Model the rats as above methods and operation steps for 12 weeks.At the same time gavage corresponding herbs to the rats of Yiqi herbs prevention group(6g/kg),Huayu herbs prevention group(4g/kg),Jianpi herbs prevention group(8g/kg) and Western medicine prevention group(Vitacoenzyme,1g/kg) .a12 weeks later,,all the rats of model group and prevention groups are executed to procure the specimens. On the other hand, Double distilled water(3ml per rat ) , Yiqi herbs (6g/kg),Huayu herbs (4g/kg),Jianpi herbs (8g/kg) and Vitacoenzyme(1g/kg) are gavaged correspondingly to model-control group,Yiqi herbs treatment group, Huayu herbs treatment group, JianpiHuayu herbs treatment group, Western medicine treatment group,12 weeks later, all the rats of model-control group and treatment groups are executed to procure the specimens.2. Observe the pathological changes of rat gastric mucosa3. Assay the changes of the expression of bcl-2 in gastric mucosa by immunohistochemical methods;Assay the reactive oxygen species(ROS)and the content of Ca²⁺ in gastric tissue by flow cytometry; Detect the changes of the expression of Caspase-3 in gastric tissue by microplate reader for enzyme activityResults: 1. The incidence of Dysplasia in the model-control group (100%) is more than that in the Jianpi herbs Prevention group(71.4%),the Huayu herbs Prevention group (66.6%), the JianpiHuayu herbs Prevention group (12.5%)and the Western medicine prevention group(62.5%).The cases of Dysplasia in Chinese medicine and Western medicine prevention group are mainly mild dysplasia,but All of the cases in Pathologic-Control group belong to moderate and severe dysplasia.The incidence of mild dysplasia in the Jianpi herbs Prevention group is 80%, in the Huayu herbs Prevention group is 50%,in the JianpiHuayu herbs Prevention group is 100%,in the Western medicine prevention group is 60%. Although 87.5% of rats in the JianpiHuayu herbs Prevention group are not sick, The incidence of mild dysplasia in each groups(the Jianpi herbs Prevention group,the Huayu herbs Prevention group and the JianpiHuayu herbs Prevention group) has no significant difference compared with the Western medicine prevention group(P>0.05).We believe that may caused by too few rats in each groups.In the process of treatment, after 12 weeks of normal feeding,the Pathological damage of gastric mucosal dysplasia in the Model-Control group have no improvement,but after 12 weeks of Gavage treatment by herbs and Vitacoenzyme, the incidence of gastric mucosal dysplasia are lower than which in the Model-Control group(P<0.05).What in each treatment groups(62.5%,55.6%,100%,50%) are mainly mild dysplasia cases, but All of the cases in Model-Control group belong to moderate and severe dysplasia(100%). Although 75% of rats in the JianpiHuayu herbs treatment group pull through, the incidence of each groups has no significant difference compared with each other in statistics(P>0.05). We believe that may caused by too few rats in each groups.2. The expression of BCL-2 gene in normal gastricmucosa and light, moderate ,severe dysplasia of gastricmucosa increased progressively with the illness grew worse. In the normal gastric mucosa, positive rate of Bcl-2 was 12.5%;In the model group and the model-control group, positive rate of Bcl-2 were 90%,87.5%,but the incidence of moderate and severe dysplasia are 100% in them. After prevention and treatment of each group by Chinese medicine or western medicine, with the decline in the degree of dysplasia, the rate of Bcl-2's expression is declining. In the prevention groups, the dysplasia's rate of Jianpi herbs group,Huayu herbs group,JianpiHuayu herbs group,and Western group are 71.4%,66.6%,12.5%,62.5%,and most concentrated in mild dysplasia,the rate are 80%, 50%, 100%, 60%.Accompanying the positive rate of the expression of Bcl-2 decline with the rate 57.1%, 55.5%, 12.5%, 50%. In the treatment group, the dysplasia's rate of Jianpi herbs group,Huayu herbs group,JianpiHuayu herbs group,and Western group are 88.8%,90%,25%,75%, mild dysplasia's rate are 62.5%, 55.6%, 100%, 50%, accompanying the positive rate of the expression of Bcl-2 are 55.5%,60%,25%,50%. And no matter prevention or treatment groups, the expression of Bcl-2 in Chinese groups and Vitacoenzyme group are less than the model group and the model-control group.And no matter prevention or treatment groups, effect of JianpiHuayu herbs group is better than YiqiJianpi herbs group and HuoxueHuayu herbs group.3. Caspase-3 of gastric mucosal cells in model group and control-model group significantly reduce, compare with the normal group are significantly different (P <0.05). In the prevention groups, the expressions of Caspase-3 increase in JianpiHuayu herbs group, JianpiYiqi herbs group, HuoxueHuayu herbs group andWestern medicine Group, compare with the model group are significantly different (P <0.05). JianpiHuayu herbs group is better than other groups,but JianpiYiqi herbs group, HuoxueHuayu herbs group and Western medicine Group compare with each other are no significantly different (P>0.05)In the treatment group, the expressions of Caspase-3 increase in JianpiHuayu herbs group, JianpiYiqi herbs group, HuoxueHuayu herbs group and Western medicine Group, compare with the model-control group are significantly different (P <0.05). JianpiHuayu herbs group is better than other groups,but JianpiYiqi herbs group, HuoxueHuayu herbs group and Western medicine Group compare with each other are no significantly different (P>0.05)4. The content of ROS and Ca²⁺ of model group obviously declined, which has significant difference compared with blank-control group (p<0.05). Either prophylaxis or treatment of drug delivery, Chinese medicine group and modern medicine group can increase the content of ROS and Ca²⁺, significantly different compared with model group(p<0.05); the effect between JianpiHuayu herbs group and modern medicine group is no difference(p>0.05), and the two groups have no significant difference compared with blank-control group(p>0.05), while the two groups have significant difference compared with Jianpi herb group and Huayu herb group (p<0.05) and get better effect than them; the effect between Jianpi herb group and Huayu herb group has no significant difference (p>0.05). From the results, it shows that the content of ROS and Ca²⁺ is the highest in the normal gastric mucosa, but the ROS and Ca²⁺ content is correspondingly minimized in model group and blank-model group in which the moderate and severe dysplasia rate is 100%. In the prophylaxis or treatment of drug delivery process, the effect of Jianpihuayu herb group is better than Jianpiyiqi herb group and Huoxuehuayu herb group (P<0.05), while Jianpiyiqi herb group and Huoxuehuayu herb group have no significant difference (P>0.05) either prophylaxis or treatment of drug delivery.Conclusion:Either prophylaxis or treatment of drug delivery, TCM with the function of Jianpihuatan, Jianpi and Huayu shows a more significant role in prevention and treatment of the gastric epithelial dysplasia. The effecting mechanism works by reducing Bcl-2 gene expression of gastric tissue, increasing reactive oxygen species (ROS), the content of Ca²⁺ and the expression of Caspase-3 in gastric tissue, effects in all aspects of apoptosis in order to increase the apoptosis and reduce cell proliferation state to achieve the treatment of atrophic gastritis with precancerous lesions of gastric cancer and prevent the canceration. In this process, that TCM with the function of Jianpihuatan, Jianpi and Huayu effect in the three segments of this test, proves TCM can take the same place in treating atrophic gastritis with precancerous lesions of gastric cancer. TCM with the function of Jianpihuatan are significantly better than the other two treating principles in the treatment of atrophic gastritis with precancerous lesions of gastric cancer, while TCM with the function of Jianpi and TCM with the function of Huayu have no significant difference in the treatment.