瓜氨酸对辐射致小鼠肠道损伤的防护作用及机制研究

Protective effect and mechanism of citrulline on intestinal injury induced by radiation in mice

电离辐射会导致动物肠道的损伤,瓜氨酸在小肠上皮细胞内合成,同时被证明对肠道具有一定的保护作用。通过构建小鼠急性辐射致肠道损伤模型,设置正常对照组、单纯辐照组以及辐照加瓜氨酸组,研究瓜氨酸的辐射防护作用及机制。实验结果表明:在辐照后连续一周腹腔注射1 g∙kg^(−1)∙d^(−1)的瓜氨酸能够显著延长受照小鼠中位生存期,增加小鼠体重,显著降低小鼠血浆内毒素含量,提高黏着斑激酶(Focal Adhesion Kinase,FAK)和肠道紧密连接(Occludin)蛋白的表达水平,同时降低一氧化氮(Nitric Oxide,NO)和诱导型一氧化氮合酶(inducible Nitric Oxide Synthase,iNOS)的表达量。本实验证明:瓜氨酸可以通过改善受照小鼠肠道屏障完整性,改善肠道屏障功能,缓解亚硝化应激,对电离辐射小鼠肠道损伤具有保护作用。

[Background]Ionizing radiation can cause damage to animal's intestinal tissue.Citrulline is produced in the intestinal epithelial cell and has been proven to possess a protective effect on the gastrointestinal tract.[Purpose]This study aims to investigate the protective effects and the underlying mechanisms of citrulline in the context of radiation-induced intestinal injuries.[Methods]Firstly,a mouse model of an acute radiation-induced intestinal injury was established,incorporating a normal control,a simple irradiation,and an irradiation plus citrulline group.Then,these groups were employed to scrutinize the protective effects and mechanisms associated with citrulline.Subsequently,hematoxylin-eosin staining was used to examine the morphology of the mice's intestinal tissue,and the Elisa kit was employed to quantify endotoxin levels in plasma,as well as nitric oxide and inducible nitric oxide synthase in the intestinal tissue.Finally,focal adhesion kinase and Occludin levels in the intestinal tissue were assessed using western blotting.[Results]The experimental results demonstrate that intraperitoneal injection of 1 g∙kg^(−1)∙d^(−1) citrulline for one week following irradiation significantly extend the median survival time of irradiated mice and increase their body weight.Moreover,it markedly reduces plasma endotoxin levels,elevate the expression levels of focal adhesion kinase(FAK)and intestinal tight junction protein(Occludin),and decreases the expression levels of nitric oxide(NO)and inducible nitric oxide synthase(iNOS)in the intestinal tissue.[Conclusions]Citrulline enhances the integrity of the intestinal barrier in irradiated mice,improves barrier function,mitigates nitrosative stress,and demonstrates a protective impact on radiation-induced intestinal damage in mice.