| Gastric cancer is the most common type of Chinese malignant tumors, the incidence and mortality rate are at the first place of digestive malignant tumors in China. Based on that, gastric cancer is a serious threat to people's health and life safe. Gastric carcinogenesis is a complex biological process that multiple factors, steps and genes involved in. The Correa model (chronic superficial gastritis→chronic atrophic gastri t is→intestinal metaplasia→dysplasia→gastric cancer) has been got widespread recognition all over the world. Intestinal metaplasia and dysplasia are called gastric precancerous lesions, which can more easily transform as cancer tissues, especially the dysplasia,60%to80%severe dysplasia patients may be developed into gastric cancers. However, the treatment of dysplasia is still relatively limited. Therefore, how to effectively intervene dysplasia, reverse gastric precancerous lesions, block the development of gastric cancer, these are hot spots for prevention and treatment of gastric cancer study at present.This study established the rat model of chronic atrophic gastritis with dysplasia, choiced Xiaopi particle (Lanceolata, Lily, Combined spicebush, Citrus medica, Salvia, Panax notoginseng powder, Zedoary turmeric, Dandelion, Hedyotis diffusa willd), which was prescripted by Yiqi Huayu Jiedu principle, as therapeutic drug and researched molecular mechanisms of Yiqi Huayu Jiedu principle treating chronic atrophic gastritis with dysplasia, reversing gastric precancerous lesions and blocking the development of gastric cancer.Objective:To observe the effects of Yiqi Huayu Jiedu principle on general situations, mortality and pathological changes of chronic atrophic gastritis with dysplasia rats. And to study the functions of this principle for tumor suppressor gene p53, proto-oncogene c-Myc and the EGFR/MAPK cell signal transduction pathway.Methods:60Wistar rats were randomly divided into making model group (50rats) and blank group (10rats). The blank group rats were given standard diet of SPF animals until the end of the experiment. Three factors were used to make model of chronic atrophic gastritis with dysplasia for the making model group rats, mainly by120μg/mL MNNG,5mL/kg,1time/d, assisted by0.1%ammonia for drinking water and0.03%ranitidine in feed. After the model was succeeded at the28th weekend, residual30rats in the making model group were randomly divided into model group, Weimeisu group and Xiaopi particle group, each group included10rats. Each group was given the corresponding medicine once daily:3mL/kg saline for the model group,2mL/kg Weimeisu suspension liquid (0.3g/kg Weimeisu) for the Weimeisu group and3mL/kg Xiaopi particle Solution (containing9g/kg crude drug). All the rats were sacrificed after treatment for12weeks. The pathological changes, p53, c-Myc, EGFR, ERK and other indexes were detected with light microscope, real-time PCR, Western blot and other means.Results:1The general situations of Xiaopi particle group and Weimeisu group rats were better than the model group, especially Xiaopi particle group. Xiaopi particle group and the blank group had no death and the lowest mortality in treatment stage;3rats died in the model group (3/10,30%);2rats died in Weimeisu group (2/10,20%). The rat body weight of the making model group was significantly lighter than the blank group (P=0.000, P<0.01); the increase of body weight of the making model group was significantly lower than the blank group (P=0.000, P<0.01).2The pathological results showed that3gastric cancers in the model group (3/7,43%), dysplasia degree in Xiaopi particle group and Weimeisu group were lighter than the model group, especially Xiaopi particle group. Five cases were already close to normal gastric mucosae (5/10,50%).3The wild-type p53mRNA expression of the model group was significantly lower than the blank group (P=0.007, P<0.01); Xiaopi particle group was higher than the model group and Weimeisu group (P=0.039and0.049, P<0.05) and had no difference with the blank group (P=0.411, P>0.05); Weimeisu group was significantly lower than the blank group (P=0.009, P<0.01) and had no difference with the model group{P=0.911, P>0.05). The protein express ion of mutant p53in the model group was significantly higher than the blank group (P=0.000, P<0.01); Xiaopi particle group was significantly lower than the model group and Weimeisu group (P=0.000and0.006, P<0.01) and had no difference with the blank group (P=0.374, P>0.05); Weimeisu group was significant ly lower than the model group (P=0.000, P<0.01) and significantly higher than the blank group (P=0.002, P<0.01).4The c-Myc mRNA expression of the model group was significantly higher than the blank group (P=0.000, P<0.01); Xiaopi particle group was significantly lower than the model group{P=0.001, P<0.01) and also lower than Weimeisu group (/"=0.025, P<0.05), compared with the blank group, they had no difference (P=0.886,P>0.05); Weimeisu group was higher than the blank group(P=0.019, P<0.05) and had no difference with the model group (P=0.066, P>0.05). The c-Myc protein expression of the model group was significantly higher than the blank group (P=0.001, P<0.01); Xiaopi part icle group was significantly lower than the model group (P=0.001, P<0.01) and compared with the blank group and Weimeisu group, they had no difference (P=0.927and0.059, P>0.05); Weimeisu group was lower than the model group (P=0.032, P<0.05) and higher than the blank group (P=0.049, P<0.05).5The EGFR protein expression of the model group was significantly higher than the blank group (P=0.000,P<0.01); Xiaopi particle group was significantly lower than the model group (P=0.000, P<0.01) and also lower than Weimeisu group (P=0.032, P<0.05), compared with the blank group, they had no difference (P=0.064, P>0.05); Weimeisu group was lower than the model group (P=0.034, P <0.05) and significantly higher than the blank group (P=0.001, P<0.01).6The ERK1/2protein expression of the model group was significantly higher than the blank group (P=0.000, P<0.01); Xiaopi particle group was significantly lower than the model group and Weimeisu group (both P=0.000, P <0.01) and significantly higher than the blank group (P=0.003, P<0.01); Weimeisu group was significantly lower than the model group (P=0.001, P<0.01) and significantly higher than the blank group (P=0.000, P<0.01). The p-ERK1/2protein expression of the model group was significantly higher than the blank group (P=0.000,P<0.01); Xiaopi particle group was significantly lower than the model group and Weimeisu group (both P=0.000, P<0.01), compared with the blank group, they had no difference (P=0.616, P>0.05); Weimeisu group was lower than the model group (P=0.010, P<0.05) and significantly higher than the blank group (P=0.000, P<0.01).Conclusion:Xiaopi particle, prescripted by Yiqi Huayu Jiedu principle, can effectively improve the general situations of chronic atrophic gastritis with dysplasia rats, reduce the mortality, reverse the pathological changes of gastric precancerous lesions and block the development of gastric cancer. Its effective mechanism may reverse mutation of p53gene, promote p53to play its original role for tumor suppression, inhibite over-expression of proto-oncogene c-Myc mRNA and its protein, reduce high expression of EGFR protein and block abnormal activation of the EGFR/MAPK cellular signal transduction pathway. |
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