番茄红素通过上调Nrf2-Ho-1/Nqo1蛋白表达治疗幽门螺杆菌相关慢性萎缩性胃炎

探讨番茄红素（LYC）对慢性萎缩性胃炎（CAG）的治疗作用及其潜在作用机制。

通过网络数据库筛选出CAG致病靶点与LYC作用靶点并取交集，通过String数据库构建蛋白互作网络，并使用Cytoscape进行可视化分析。最后通过对LYC治疗CAG可能核心靶点基因进行GO功能和KEGG通路富集分析筛选关键通路进行实验验证。构建CAG实验小鼠模型，在LYC干预后通过H&;E染色、ELISA、免疫组织化学染色、RT-qPCR检测及Western Blot等实验方法评估LYC对CAG的治疗作用及其可能作用机制。

LYC与CAG共同靶点77个，通过GO功能和KEGG通路富集分析发现主要涉及的通路有氧化应激反应、对活性氧的反应等。使用KEGG Pathview绘制Chemical carcinogenesis-reactive oxygen species通路途径，发现ROS-Nrf2-Ho-1/Nqo1通路作用较为显著。H&;E染色和血清胃泌素结果提示CAG小鼠模型构建成功；与模型组相比，LYC干预后小鼠血清胃泌素水平较模型组显著下降，胃黏膜萎缩程度显著减轻，小鼠胃组织中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶抗氧化蛋白水平显著上调，丙二醛水平显著下降；免疫组化、RT-qPCR检测及Western Blot结果共同提示与模型组相比，LYC干预后小鼠胃组织中Nrf2、Ho-1、Nqo1 mRNA和蛋白水平显著上调。

LYC可通过提高小鼠胃黏膜抗氧化应激能力以及上调ROS-Nrf2-Ho-1/Nqo1通路蛋白表达从而发挥治疗CAG的目的。

Lycopene treats chronic atrophic gastritis by up regulating the expression of Nrf2-Ho-1/Nqo1 protein

ObjectiveTo observe the therapeutic effect of lycopene (LYC) on chronic atrophic gastritis (CAG) and its potential mechanism. MethodsThe pathogenic target of CAG and the target of LYC were screened and intersected by searching the network database. The protein interaction network was constructed through String database, and the visual analysis was performed by using Cytoscape. Finally, we screened the key pathway through GO function and KEGG pathway enrichment analysis of the core target gene of LYC in the treatment of CAG. The experimental mouse model of CAG was established. After the intervention of LYC, the therapeutic effect of LYC on CAG and its possible mechanism were evaluated with H&E staining, ELISA, immunohistochemical staining, RT-qPCR detection, Western Blot and other experimental methods. ResultsThere were 77 co-action targets of LYC and CAG. The analysis of GO function and KEGG pathway enrichment found that the main pathways involved were oxidative stress response and response to reactive oxygen species, etc. Using KEGG Pathview to plot the Chemical carcinogenesis-reactive oxygen species pathway, we found that ROS-Nrf2-Ho-1/Nqo1 pathway played a more significant role. The H&E staining and serum gastrin results indicated that the mouse model of CAG was successfully constructed. Compared with the model group, the serum gastrin concentration of mice after LYC intervention was significantly lower than that in the model group, the degree of gastric mucosal atrophy was significantly reduced, the levels of SOD, CAT and GSH-Px antioxidant protein in the gastric tissue of mice significantly increased, and the level of MDA significantly decreased. Immunohistochemistry, RT-qPCR and Western Blot showed that the levels of Nrf2, Ho-1, Nqo1 mRNA and protein in gastric tissue of mice after LYC intervention significantly increased compared with the model group. ConclusionLYC can play a role in the treatment of CAG by increasing the ability of gastric mucosa to resist oxidative stress and up regulating the expression of ROS-Nrf2-Ho-1/Nqo1 pathway protein in mice.