胃痞灵通过Nrf2/NQO1/HO-1信号通路调控胃“炎-癌”转化氧化应激机制

Mechanism of Weipiling regulating the oxidative stress of transformation of gastric‘inflammation to cancer’via Nrf2/NQO1/HO-1 signaling pathway

目的:探讨胃痞灵在体内抑制胃“炎-癌”转化氧化应激的作用机制。方法:50只Ba l b/c小鼠分为空白组(10只)及造模组[40只,其中模型组,胃痞灵高、低剂量组,阳性药组(维生素B_(12)),各10只],构建胃癌前病变小鼠模型,使用相应药物干预后,观察小鼠整体情况(尾巴、体型)、体质量增长情况、胃黏膜组织结构变化、检测核因子E2相关因子2(Nrf2)/醌氧化还原酶1(NQO1)/血红素加氧酶-1(HO-1)信号通路相关蛋白、基因表达及血清SOD值。结果:与空白组比较,模型组小鼠尾巴细短、色泽较瘀暗,体型明显减小,体质量增长缓慢,胃黏膜组织细胞异型增生明显,胃黏膜Nrf2/NQO1/HO-1信号通路被激活;与模型组比较,胃痞灵高、低剂量组小鼠整体情况改善,胃黏膜组织结构重塑、异型增生减少,且Nrf2/NQO1/HO-1信号通路受到一定程度抑制(表达增多),提示氧化应激被阻断。结论:MNNG自由饮用可诱导小鼠胃黏膜上皮发生氧化应激,胃痞灵可能在一定程度阻断氧化应激进而抑制胃“炎-癌”转化,从而发挥抗胃癌前病变的作用。

Objective:To explore the mechanism of Weipiling in inhibiting the oxidative stress of gastric‘inflammation cancer’transformation in vivo.Methods:A total of 50 Balb/c mice were divided into normal group(10 mice)and model group[40 mice,model group,high-and low-dose group of Weipiling,positive drug group(vitamin B_(12)),10 mice in each group].The model of precancerous lesions of gastric cancer were established.After the treatment with corresponding drugs,the overall situation(tail,body shape),body mass growth,and changes in the structure of gastric mucosa were observed.Nuclear factor E2 related factor 2(Nrf2)/quinone oxidoreductase 1(NQO1)/heme oxygenase-1(HO-1)signal pathway related protein,gene expression and serum SOD value were detected.Results:Compared with the blank group,the tail of the model group was shorter,the color was darker,the body size was significantly reduced,the body mass increased slowly,the gastric mucosa tissue cell dysplasia was obvious,and the gastric mucosa Nrf2/NQO1/HO-1 signal pathway was activated;Compared with the model group,the overall situation of mice in the high-and low-dose groups of Weipiling improved,the structural remodeling and dysplasia of gastric mucosa decreased,and the Nrf2/NQO1/HO-1 signal pathway was inhibited to a certain extent(increased expression),suggesting that oxidative stress was blocked.Conclusion:Free drinking of MNNG can induce oxidative stress in the gastric mucosa epithelium of mice.Weipiling may block oxidative stress to a certain extent and then inhibit the transformation of gastric‘inflammation to cancer’,thus playing an anti-gastric precancerous role.