基于AKT/mTOR通路探究养阴活胃方对慢性萎缩性胃炎大鼠模型自噬的影响  

To explore the effects of Yangyin Huowei Decoction on autophagy in rats model with chronic atrophic gastritis(CAG)based on protein kinase B(AKT)/mammalian Target of Rapamycin(mTOR)pathway

作　　者：王宏宇 谢姗珊 邵昌明 智勇[1] 樊郑阳 郑帅 王雯[3] 曾斌芳[1] WANG Hongyu;XIE Shanshan;SHAO Changming;ZHI Yong;FAN Zhengyang;ZHENG Shuai;WANG Wen;ZENG Binfang(College of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830011,China;Xinjiang Key Laboratory of Mental Development and Learning Sciences,Xinjiang Normal University,Urumqi 830017,China;People′s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)

机构地区：[1]新疆医科大学中医学院,乌鲁木齐830011 [2]新疆师范大学新疆心智发展与学习科学重点实验室,乌鲁木齐830017 [3]新疆维吾尔自治区人民医院,乌鲁木齐830001

出　　处：《新疆医科大学学报》2025年第4期530-537,共8页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区科学技术厅,区域协同创新专项-上海合作组织科技伙伴计划及国际科技合作计划项目(2022E01008);新疆医科大学研究生创新创业项目(CXCY2023012)。

摘　　要：目的基于蛋白激酶B(Protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)通路探讨养阴活胃方对慢性萎缩性胃炎大鼠模型自噬的影响。方法选取雄性SD大鼠50只为研究对象,10只作为空白组,其余40只采用N-甲基-N′-硝基-N-亚硝基胍(N-methyl-N′-nitro-N-nitrosoguanidine,MNNG)以及饥饱失常法造模,持续10周,建立CAG大鼠模型。造模成功后将模型大鼠随机分为模型组(1 mL/100 g生理盐水灌胃)、养胃舒组(养胃舒颗粒0.25 g/kg灌胃)、养阴活胃方组(22.62 g/kg养阴活胃方饮片量灌胃),空白组不进行干预,其余各组每天灌胃1次,持续8周。观察各组大鼠表征、检测胃液酸碱度(Power of hydrogen,pH),酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)检测血清白细胞介素-1β(Inter leukin-1 beta,IL-1β)、白细胞介素-6(Inter leukin-6,IL-6)含量;苏木精-伊红(Hematoxylin-eosin,HE)染色观察胃组织病理变化;免疫组织化学法(Immuno histochemistry,IHC)检测胃黏膜AKT、mTOR蛋白阳性表达面积,蛋白免疫印迹法(Western blot,WB)检测胃黏膜AKT、mTOR、Beclin-1、LC3B蛋白表达量情况。结果与空白组比较,模型组胃液pH值、IL-1β、IL-6、AKT、mTOR均升高(P<0.05);模型组大鼠体重、胃壁厚度、Beclin-1、LC3B明显降低(P<0.05),且HE染色显示胃黏膜出现明显萎缩、炎症、肠化。与模型组比较,养胃舒组及养阴活胃方组胃液pH值、IL-1β、IL-6、AKT、mTOR均降低(P<0.05),体重、胃壁厚度、Beclin-1、LC3B蛋白均升高(P<0.05),且HE染色显示胃黏膜萎缩、炎症减轻。与养胃舒组比较,养阴活胃方组IL-1β、AKT、mTOR、Beclin-1蛋白表达水平均降低(P<0.05),LC3B蛋白表达量明显增加(P<0.05)。结论养阴活胃方能有效改善CAG模型大鼠胃黏膜的病理状况,抑制AKT/mTOR通路,激活或增强细胞自噬,达到治疗CAG的作用。Objective Based on the protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway,to explore the effect of Yangyin Huowei Decoction on autophagy in rats model with chronic atrophic gastritis(CAG).Methods A total of 50 male SD rats were selected as the research objects,10 rats were used as the blank group,and the remaining 40 rats were modeled by N-methyl-N′-nitro-N-nitrosoguanidine MNNG and abnormal hunger and satiety.The CAG rat model was established by continuous intervention for 10 weeks.After successful modeling,the model rats were randomly divided into model group(1 mL/100 g normal saline gavage),Yangweishu group(0.25g/kg Yangweishu granule gavage)and Yangyinhuowei group(22.62 g/kg Yangyinhuowei decoction gavage).The blank group did not intervene,and the other groups were gavaged once a day for 8 weeks.The characterization of rats in each group was observed,the pH value of gastric juice was detected,and the contents of serum interleukin-1β(IL-1β)and interleukin-6(IL-6)were detected by Enzyme-Linked Immunosorbent Assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of gastric tissue.Immunohistochemistry(IHC)was used to detect the positive expression area of AKT and mTOR protein in gastric mucosa,and Western blot(WB)was used to detect the expression of AKT,mTOR,Beclin-1 and LC3 B protein in gastric mucosa.Results Compared with the blank group,the pH value of gastric juice,IL-1β,IL-6,AKT and mTOR in the model group was increased(P<0.05).The body weight,gastric wall thickness,Beclin-1 and LC3 B in the model group were significantly decreased(P<0.05).HE staining showed that the gastric mucosa showed obvious atrophy,inflammation and intestinal metaplasia.Compared with the model group,the pH value of gastric juice,IL-1β,IL-6,AKT and mTOR in the Yangweishu group and the Yangyin Huowei Decoction group was decreased(P<0.05).The body weight,gastric wall thickness,Beclin-1 and LC3 B protein of rats were increased(P<0.05).HE staining showed that gastric mucosal atrophy and i

关 键 词：养阴活胃方 慢性萎缩性胃炎 AKT/mTOR通路 自噬 

分 类 号：R259[医药卫生—中西医结合]