基于AMPK/mTOR信号通路介导的自噬途径研究黄芪多糖对急性放射性肠炎大鼠肠黏膜的保护作用

目的：探究基于AMP活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路介导的自噬途径研究黄芪多糖（APS）对急性放射性肠炎大鼠肠黏膜的保护作用。方法：对SD大鼠进行12 Gy单次照射，制备急性放射性肠炎模型，随机分为模型组、APS(2 g/kg)组、AMPK抑制剂compound C(CC,0.2 mg/kg)组和APS(2 g/kg)+CC(0.2 mg/kg)组，每组12只；另取12只大鼠不做处理，设为对照组。以药物分组干预处理后，检测大鼠一般情况，做临床症状评分；HE染色观察大鼠肠黏膜病理形态；试剂盒检测大鼠血清白细胞介素17(IL-17)、IL-1β、肿瘤坏死因子α（TNF-α）、肠型脂肪酸结合蛋白（I-FABP）、细胞间黏附分子1(ICAM-1)和二胺氧化酶（DAO）水平；Western blot法检测大鼠肠黏膜组织自噬相关蛋白（beclin-1和LC3-II/LC3-I）及AMPK/mTOR通路相关蛋白（p-AMPK/AMPK和p-mTOR/mTOR）水平。结果：与对照组相比，模型组大鼠肠黏膜组织出现严重病理损伤，肠黏膜组织beclin-1、LC3-II/...

Astragalus polysaccharide protects against intestinal mucosal injury in rats with acute radiation enteritis through AMPK/mTOR-mediated autophagy pathway

AIM:To explore the the protective effect of Astragalus polysaccharide(APS)on intestinal mucosa in rats with acute radiation enteritis through AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)-mediated autophagy pathway.METHODS:Forty-eight SD rats were irradiated at a single dose of 12 Gy to prepare an acute radiation enteritis model,and were randomly divided into model group,APS(2 g/kg)group,AMPK inhibitor compund C(CC,0. 2 mg/kg)group and APS(2 g/kg)+CC(0. 2 mg/kg)group,with 12 rats in each group. Another 12 rats without treatment served as control group. The general condition of the rats was checked,and the clinical symptoms were scored after treatment. HE staining was used to detect the pathomorphological changes of rat intestinal mucosa. Kits were used to detect the serum levels of interleukin-17(IL-17),IL-1β,tumor necrosis factor-α(TNF-α),intestinal fatty acid-binding protein(I-FABP),intercellular adhesion molecule-1(ICAM-1)and diamine oxidase(DAO). Western blot was used to detect the levels of autophagy-related proteins(beclin-1 and LC3-II/LC3-I)and AMPK/mTOR pathway-related proteins(p-AMPK/AMPK and p-mTOR/mTOR)in rat intestinal mucosal tissue.RESULTS:Compared with control group,the intestinal mucosal tissue in model group showed severe pathological damage,the levels of beclin-1,LC3-II/LC3-I and p-AMPK/AMPK in the intestinal mucosal tissue were significantly decreased(P<0. 05),and the clinical symptom score,serum IL-17,IL-1β,TNF-α,I-FABP,ICAM-1 and DAO levels,and intestinal mucosal tissue p-mTOR/mTOR level were significantly increased(P<0. 05). Compared with model group and APS+CC group,the pathological damage of the intestinal mucosa in APS group was reduced,the levels of beclin-1,LC3-II/LC3-I and p-AMPK/AMPK in the intestinal mucosal tissue were increased(P<0. 05),and the clinical symptom score,serum IL-17,IL-1β,TNF-α,IFABP and DAO levels,and intestinal mucosal tissue p-mTOR/mTOR level were decreased(P<0. 05). The pathological damage of the intestinal mucosa in CC group was aggravated,and the trends of various indexes were opposite to those in APS group(P<0. 05).CONCLUSION:Astragaluspolysaccharide enhances the autophagy by activating AMPK/mTOR signaling pathway,reduces the inflammatory injury of intestinal mucosa in rats with acute radiation enteritis,and protect the intestinal function.