机构地区:[1]延安大学附属医院,陕西延安716000 [2]延安大学医学院基础医学教研室,陕西延安716000
出 处:《中医药导报》2021年第10期32-36,41,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy
基 金:陕西省重点研发计划项目(2019SF-310)。
摘 要:目的:探究理中汤对慢性萎缩性胃炎模型大鼠胃黏膜的保护作用及对ADAM17、EGFR蛋白的调节作用。方法:72只大鼠随机选取12只作为对照组,其余大鼠采用N-甲基-N-硝基-N-亚硝基胍(MNNG)溶液联合饥饱失常饮食控制法及雷尼替丁灌胃法建立慢性萎缩性胃炎大鼠模型,将造模成功的大鼠随机分为模型组、维酶素组、理中汤低剂量组、理中汤中剂量组、理中汤高剂量组。各给药组大鼠灌胃给予相应药物,对照组及模型组大鼠灌胃给予等体积生理盐水,1次/d,连续10周。测定给药前后大鼠体质量变化,使用ELISA试剂盒测定大鼠血清胃泌素(GAS)、血浆胃动素(MTL)水平,以及胃组织IL-1β、IL-8、IL-12水平;HE染色法观察胃黏膜病理学变化,采用RTq-PCR测定胃组织EGFR mRNA、ADAM17 mRNA表达水平,免疫印迹法测定胃组织EGFR、ADAM17蛋白水平。结果:与对照组比较,模型组大鼠体质量、血清GAS水平及血浆MTL水平均明显降低(P<0.05),胃黏膜组织IL-1β、IL-8、IL-12水平,胃黏膜EGFR mRNA、ADAM17 mRNA表达水平,以及胃黏膜EGFR、ADAM蛋白水平均明显升高(P<0.05),模型组大鼠胃黏膜组织发生炎症性改变;与模型组比较,理中汤低、中、高剂量组及维酶素组大鼠给药后体质量、血清GAS水平及血浆MTL水平明显升高(P<0.05),胃黏膜组织IL-1β、IL-8、IL-12水平,胃黏膜EGFR mRNA、ADAM17 mRNA表达水平,以及胃黏膜EGFR、ADAM蛋白水平明显降低(P<0.05),大鼠胃黏膜组织病理学改善,且各项指标变化与理中汤剂量有依赖性;与维酶素组比较,理中汤高剂量组大鼠体质量、血浆MTL水平明显升高(P<0.05),胃黏膜组织IL-8、IL-12水平,胃黏膜EGFR mRNA、ADAM17 mRNA表达水平,以及胃黏膜EGFR、ADAM蛋白水平明显降低(P<0.05)。结论:理中汤能够修复慢性萎缩性胃炎大鼠胃黏膜损伤,恢复胃黏膜功能,抑制慢性萎缩性胃炎病理进展,其机制可能与调节ADAM17及EGFR蛋白水平有关。Objective:To study the protective effect of Lizhong Decoction on gastric mucosa and regulation of ADAM17 and EGFR proteins in rats with chronic atrophic gastritis.Methods:Totally 12 rats were selected as control group from 72 rats,and the rest were established chronic atrophic gastritis model by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution combined with hunger and satiety disorder diet control method and ranitidine intragastric administration.The Successful modeling rat s were randomly divided into model group,vitacoenzyme group,Lizhong Decoction low dose group,Lizhong Decoction middle dose group and Lizhong Decoction high dose group.The rats were given the corresponding drugs by gavage respectively in each administration group,and the rats in the control group and the model group were given the same volume of normal saline by gavage,once a day,for 10 consecutive weeks.The body weight of rats was measured before and after treatment.The levels of serum gastrin(GAS),plasma motilin(MTL)and gastric tissue IL-1β,IL-8,IL-12 were determined by enzyme linked immunosorbent assay(ELISA).The pathological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining.The levels of EGFR mRNA and ADAM17 mRNA in gastric tissue were measured by real-time quantitative polymerase chain reaction(RTq-PCR)and the protein levels of EGFR and ADAM17 in gastric tissue were measured by immunoblotting.Results:Compared with the control group,the body weight,serum GAS level and plasma MTL level significantly reduced in model group(P<0.05),and the levels of IL-1β,IL-8 and IL-12 in gastric mucosa,EGFR mRNA and ADAM17 mRNA in gastric mucosa,as well as protein levels of EGFR and ADAM17 in gastric tissue significantly increased in model group(P<0.05).And gastric mucosal tissues showed inflammatory changes in model group.Compared with rats in the model group,the body weight,serum GAS level and plasma MTL level significantly increased in Lizhong Decoction low dose group,Lizhong Decoction middle dose group,Lizhong Decoction high do
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