Experimental Effect Of Jian Pi Huo Xue Principle On Precancerous Lesions Of Gastric Cancer Rats

Objective methods:By observing the impact of Jianpi Huoxue Principle on precancerous lesions of gastric cancer(PLGC) rats’gastric mucosal pathological histology, the variance from mutL homolog1(MLH1), mut-s homologue2(MSH2),CD44V6, cyclooxygenase-2(COX-2) and matrix metalloproteinase-2(MMP-2) expression, investigate the probable mechanism of Jianpi Huoxue Principle on the prevention and treatment of PLGC and lay the foundation for further study of Jianpi Huoxue Decoction.Research methods:Experiment one:Except for the normal group, the PLGC model was established mainly through N-methyl-N-nitro N-nitrosoguanidine(MNNG) together with0.3g·L-1ranitidine,400mL·L-1alcohol and irregular diet for12weeks. During this periods, the body weight and food consumption of rats were checked weekly.2rats respectively chosen from the normal group and6rats respectively chosen from the model group were sacrificed at the end of the12th week. The samples of stomachs were removed to observe the pathological change of rats.Experiment two:The40rats after modeling were randomly divided into the model control group(0.9%Normal saline, NS), the Weifuchun group(0.86g·kg-1),the high-dose, middle-dose and low-dose of Jianpi Huoxue decoction groups(32,16,8g·kg-1),8rats for each group. Each group was given proper medicines(10mL·kg-1) administered once a day,and the normal group was given0.9%NS once a day,The above-mentioned way was kept for12weeks. During this periods, the body weight of rats were checked. All of the rats were sacrificed at the end of the experiment. The samples of stomachs were removed to observe the pathological change of rats.The expression of CD44V6,MLH1and MSH2,COX-2and MMP-2was detected by rapid immunohistochemistry.Research result:Experiment one:The rats in the model group were emaciating,less active,shineless in haris and poor in appetite.The body weight of model group rats increased much more slowly than that of the control group (P<0.01), gastric mucosa epithelial degeneration, lamina propria lymphocytes, plasma cell infiltration, glandular atrophy, Dysplasia(Dys) and local intestinal metaplasia.Experiment two:1.The change in general conditions: The rats in the model group were emaciating,less active,shineless in haris and poor in appetite.The appetite,body weight,clothing hair,stool and so on of the rats could be improved. In comparison to the model group,the body weight was significantly decreased in the Jianpi Huoxue Decoction groups and the Weifuchun group (P<0.01).But there had no significant difference between the Weifuchun group and the Jianpi Huoxue decoction groups (P>0.05).2.The change in pathology:In comparison to the model group,the incidence of intestinal metapasia(IM), Dysplasia(Dys), erosion formation and the infiltration of inflammatory cells were significantly decreased in the Jianpi Huoxue Decoction groups and the Weifuchun group(P<0.01or P <0.05),respectively. But there had no significant difference between the Weifuchun group and the Jianpi Huoxue decoction groups (P>0.05).3.The change of MLH1、MSH2、CD44V6、COX-2and MMP-2oncogene proteinexpression:①MLH1、MSH2:In comparison to the normal group, the MLH1and MSH2expression were significantly decreased in the model group(P<0.01), respectively. In comparison to the model group, the MLH1and MSH2expression were significantly increased in the high-dose, middle-dose and low-dose of Jianpi Huoxue decoction groups (P<0.01or P<0.05), respectively. And in comparison to the model group, the MSH2expression were significantly increased in the Weifuchun group (P<0.05),but the MLH1expression had no significant difference(P>0.05). In comparison to the Weifuchun group, the MLH1expression was increased in the high-dose of Jianpi Huoxue Decoction groups (P<0.05), but there were no significant difference between the Weifuchun group, the middle-dose and low-dose of Jianpi Huoxue decoction groups (P>0.05). And in the MSH2expression, there were no significant difference between the Weifuchun group and all of Jianpi Huoxue decoction groups(P>0.05).②CD44V6:In comparison to the normal group, the CD44V6expression was significantly increased in the model group(P<0.01).In comparison to the model group, the CD44V6expression was significantly decreased in the high-dose, middle-dose of Jianpi Huoxue Decoction groups(P<0.01or P<0.05), respectively. But in comparison to the model group there were no significant difference between the low-dose of Jianpi Huoxue decoction group and the Weifuchun group(P>0.05). In comparison to the Weifuchun group, the CD44V6expression was decreased in the high-dose of Jianpi Huoxue decoction groups (P<0.01). But there were no significant difference between the Weifuchun group, the middle-dose and low-dose of Jianpi Huoxue decoction groups (P>0.05).(3)COX-2and MMP-2:In comparison to the normal group, the COX-2and MMP-2expression was significantly increased in the model group(P<0.01), respectively.In comparison to the model group, the COX-2and MMP-2expression were significantly decreased in the high-dose, middle-dose and low-dose of Jianpi Huoxue Decoction groups (P<0.01or P<0.05), respectively.In comparison to the Weifuchun group, the COX-2and MMP-2expression were decreased in the high-dose of Jianpi Huoxue Decoction groups (P<0.05), but had no significant difference in the middle-dose and low-dose of Jianpi Huoxue Decoction groups (P>0.05).Research conclusion:Experiment one:The PLGC model was made successfully.Experiment two:Jianpi Huoxue decoction could improve the general conditions and improve the gastric lesions of the PLGC rats.The therapeutic effect of Jianpi Huoxue decoction for PLGC rats is associated with the decreasing of CD44V6、COX-2and MMP-2expression and increasing of MLH1and MSH2expression in gastric mucosa.