苓桂术甘汤对慢性萎缩性胃炎大鼠胃黏膜及ADAM17/EGFR通路影响研究  

Effects of Ling-Gui-Zhu-Gan Decoction on gastric mucosa repair and ADAM17/EGFR pathway regulation in rats with atrophic gastritis

作　　者：张玲 曾微微 羊章凯 麦联任 ZHANG Ling;ZENG Weiwei;YANG Zhangkai;MAI Lianren(Hainan Provincial Hospital of Traditional Chinese Medicine,Haikou 570000,Hainan,China)

机构地区：[1]海南省中医院,海南海口570000

出　　处：《现代中西医结合杂志》2023年第16期2233-2240,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：海南省卫生健康行业科研项目(22A200115)。

摘　　要：目的研究苓桂术甘汤对慢性萎缩性胃炎大鼠胃黏膜及去整合素金属蛋白酶17(ADAM17)/表皮生长因子受体(EGFR)通路的影响。方法取63只雄性SD大鼠,随机选10只作为正常对照组,其余大鼠采用1-甲基-3-硝基-1-亚硝基胍(MNNG)联合饥饱失常法建立慢性萎缩性胃炎模型。将造模成功大鼠随机分为萎缩性胃炎组,维酶素组及苓桂术甘汤低、中、高剂量组,每组10只。苓桂术甘汤低、中、高剂量组分别按照1.8 g/kg、3.6 g/kg、7.2 g/kg灌胃给予大鼠苓桂术甘汤,维酶素组按照0.2 g/kg灌胃给予维酶素,萎缩性胃炎组及正常对照组灌胃给予生理盐水,均1次/d,连续30 d。测定造模完成后及灌胃结束后大鼠体重,酶联免疫吸附法(ELISA)测定血清胃泌素(GAS)、胃动素(MTL)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)水平及胃黏膜组织中一氧化氮(NO)、P选择素(SELP)、白细胞内皮细胞黏附分子-1(LECAM-1)、内皮素-1(ET-1)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)含量,酸碱滴定法测定胃液酸度,比色法测定胃蛋白酶活性,HE染色法观察胃组织病理学形态,RT-PCR法测定胃黏膜组织中表皮生长因子(EGF)、EGFR、ADAM17 mRNA表达情况,Western blot法测定胃黏膜组织中EGF、EGFR、ADAM17蛋白表达情况。结果与正常对照组比较,萎缩性胃炎组大鼠体重、血清GAS及IL-10水平、胃液酸度及胃蛋白酶活性、胃黏膜组织中SOD及GSH-Px含量均明显降低(P均<0.05);血清MTL、TNF-α、CRP、IL-1β水平,胃黏膜组织中NO、SELP、LECAM-1、ET-1、MDA含量和EGF、EGFR、ADAM17 mRNA及蛋白表达量均明显升高(P均<0.05);胃黏膜组织病理性改变。与萎缩性胃炎组比较,苓桂术甘汤各组及维酶素组大鼠体重、血清GAS及IL-10水平、胃液酸度及胃蛋白酶活性、胃黏膜组织中SOD及GSH-Px含量均明显升高(P均<0.05);血清MTL、TNF-α�Objective It is to study the effects of Ling-Gui-Zhu-Gan Decoction(LGZGD)on gastric mucosa and adisintegrin and metalloproteinase17(ADAM17)/epidermal growth factor receptor(EGFR)pathway in rats with chronic atrophic gastritis.Methods Sixty-three male SD rats were taken,in which 10 rats were randomly selected as normal control group,and the rest rats were modeled using 1-methyl-3-nitro-1-nitrosoguanidine(MNNG)combined with starvation and satiety disorders method to establish models of chronic atrophic gastritis.The successfully modeled rats were randomly divided into atrophic gastritis group,vinblastine group,and low,medium,and high dose group of LGZGD,with 10 rats in each group.The rats in the low,medium and high do se groups of LGZGD were given LGZGD 1.8 g/kg,3.6 g/kg and 7.2 g/kg by gavage,respectively,the rats in the vinblastine group was given vinblastine 0.2 g/kg by gavage,and the rats in the atrophic gastritis group and control group were given normal saline by gavage,all once daily,continuously treated for 30 days.The body weights of the rats were measured after modeling and at the end of gavage,the levels of gastrin(GAS),gastric turbin(MTL),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-1β(IL-1β),interleukin-10(IL-10)in serum,and the contents of nitric oxide(NO),P-selectin(SELP),leukocyte endothelial cell adhesion molecule-1(LECAM-1),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in gastric mucosa tissue were determined by ELISA,the acidity of gastric juice was determined by acid-base titration,the activity of pepsin was determined by colorimetric assay,and the pathological morphology of gastric tissues was observed by HE staining,the expressions of epidermal growth factor(EGF),EGFR,ADAM17 mRNA in gastric mucosal tissue were detected by RT-PCR method,the expressions of EGF,EGFR,ADAM17 protein in gastric mucosal tissues were detected by Western blot method.Results Compared with the normal control group,the body weight,the levels o

关 键 词：慢性萎缩性胃炎 苓桂术甘汤 去整合素金属蛋白酶17 表皮生长因子受体 

分 类 号：R-332[医药卫生]