目的观察益气化瘀解毒法对慢性萎缩性胃炎(CAG)伴异型增生(Dys)模型大鼠EGFR/MAPK信号通路的影响。方法 60只SPF级健康雄性Wistar大鼠随机分为空白组10只,造模组50只。空白组给予SPF级动物标准饮食喂养,持续至实验结束。造模组采用以120 mg/L的N-甲基-N'-硝基-N-亚硝基胍(MNNG)溶液灌胃,每只5 mL/kg,1次/d为主,配合自由饮用0.1%氨水溶液及进食含0.03%雷尼替丁的颗粒状饲料,3种因素联合建立CAG伴Dys大鼠模型。28周末造模成功后将造模组剩余的30只大鼠随机分为模型组、维酶素组、益气化瘀解毒法组(中药组),每组各10只,均给予SPF级动物标准饮食喂养,并且每天灌胃1次,维酶素组予维酶素悬浊液2 mL/kg(即维酶素0.3 g/kg),中药组予益气化瘀解毒中药3 mL/kg(含生药9 g/kg),模型组予生理盐水3mL/kg。12周后即实验第40周末处死全部大鼠。选用Western blot法对各组大鼠胃窦部黏膜组织中EGFR、ERK1/2、p-ERK1/2蛋白表达进行检测。结果模型组EGFR蛋白表达最高,其次是维酶素组、中药组、空白组;其中,模型组与空白组和中药组比较均有显著性差异(均P〈0.01),中药组与维酶素组比较有显著性差异(P〈0.05)、与空白组比较无显著性差异(P〉0.05)。模型组ERK1/2蛋白表达最高,其次是维酶素组、中药组、空白组;其中,模型组、维酶素组与空白组和中药组比较均有显著性差异(均P〈0.01),中药组与空白组比较也有显著性差异(P〈0.01)。模型组p-ERK1/2蛋白表达最高,其次是维酶素组、中药组、空白组;其中,模型组与空白组和中药组比较均有显著性差异(均P〈0.01),中药组与维酶素组有显著性差异(P〈0.01)、与空白组比较无显著性差异。结论益气化瘀解毒法可显著抑制EGFR的高表达及EGFR/MAPK细胞信号转导通路的异常激活,这可能是其治疗CAG伴Dys、逆转胃癌前病变(PLGC)、防?
Objective To observe the effects of Yiqi Huayu Jiedu method on EGFR / MAPK signal pathway in rats with chronic atrophic gastritis exhibiting dysplasia. Methods 60 Wistar rats were randomly divided into model group( n = 50) and blank control group( n = 10). The blank control group rats were given standard SPF animal diet throughout the study. Three measures were combined to establish model of chronic atrophic gastritis with dysplasia,including intragastric administration of 120μg /mL MNNG,5 mL /kg,1 time /d,assisted by 0. 1% ammonia drinking water and 0. 03% ranitidine in feed. After the model was successfully established at the 28 th week,30 modeled rats were randomly divided into model group,vitacoenzyme group and Yiqi Huayu Jiedu group,with 10 rats in each group.Each group was given the corresponding medicine once daily: 3 mL / kg saline for the model group,2mL / kg vitacoenzyme suspension liquid( 0. 3 g / kg vitacoenzyme) for the vitacoenzyme group and 3 mL /kg herbal solution( containing 9 g / kg crude herb). All the rats were sacrificed after 12 weeks. The method of Western blot was used for measuring the protein expression of EGFR,ERK1 /2,and p-ERK1 /2 in rats of all groups. Results The EGFR protein expression of the model group was higher than that in the vitacoenzyme group,the Yiqi Huayu Jiedu group,and the blank group( P = 0. 000); it was significantly lower in Yiqi Huayu Jiedu group than the model group( P = 0. 000) and also lower than vitacoenzyme group( P〈0. 05). Compared with the blank control group,there was no difference( P〈0. 05). The ERK1 /2 protein expression of the model group was higher than that in the vitacoenzyme group,the Yiqi Huayu Jiedu group,and the blank group( P = 0. 000) in a descending order; it was significantly lower in Yiqi Huayu Jiedu group than the model group and vitacoenzyme group( both P = 0. 000) and significantly higher than the blank group( P〈0. 01). The p-ERK1 /2 protein expression of the model group was significantly