维生素C转运蛋白1对溃疡性结肠炎小鼠结肠组织氧化应激和炎症的改善作用OA

Objective To observe the ameliorative effects of sodium-dependent vitamin C transporter 1(SVCT1)on oxidative stress and inflammatory response in colon tissues of mice with ulcerative colitis(UC).Methods Fifty male C57BL/6J mice were selected,among which 10 mice were normally fed as the control group(Ctrl group),and the other 40 mice were used to establish the UC models.After successful modeling,the mice were randomly divided into the SVCT1 overexpression treatment group(Model+LV-SVCT1 group),overexpression empty vector treatment group(Model+LV-Null group),SV CT1 overexpression combined with quercetin(QUE,SVCT1 inhibitor)treatment group(Model+LV-SVCT1+QUE group)and model group(Model group),with 10 mice in each group.Mice in the Model+LV-SVCT1 group,Model+LV-Null group and Model+LV-SVCT1+QUE group were injected with 200 μL of SVCT1 lentivirus overexpression vector,empty vector LV-Null,and mixture of SVCT1 lentivirus overexpression vector and 10 mg/kg QUE via the tail vein,respec-tively.The three groups were injected once a day for 7 consecutive days,and the Model group received no treatment.The mice were euthanized after the last injection,and the colon tissues were collected.The mRNA and protein levels of SVCT1,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the colon tissues of each group were detected by quantitative real-time polymerase chain reaction(qPCR)and Western blotting,respectively.Meanwhile,the oxidative stress indexes including malondialdehyde(MDA),nitric oxide(NO),reactive oxygen species(ROS)and superoxide dismutase(SOD)in the colon tissues of each group were measured.Results Compared with the Ctrl group,the relative mRNA and protein expression levels of SVCT1 were significantly lower,the relative mRNA and protein expres-sion levels of IL-1β,IL-6 and TNF-α were significantly higher,the expression levels of MDA and ROS increased,while the expression levels of NO and SOD decreased in the colon tissues of the Model group(all P＜0.05).Compared with the Model+LV-Null group,the relative mRNA and protein expression levels of SVCT1 were significantly up-regulated,the rela-tive mRNA and protein expression levels of IL-1β,IL-6 and TNF-α were significantly down-regulated,the expression levels of MDA and ROS decreased,while the expression levels of NO and SOD increased in the colon tissues of the Model+LV-SVCT1 group(all P＜0.05).Compared with the Model+LV-SVCT1 group,the relative mRNA and protein expression levels of SVCT1 were significantly lower,the relative mRNA and protein expression levels of IL-1β,IL-6 and TNF-α were signifi-cantly higher,the expression levels of MDA and ROS increased,while the expression levels of NO and SOD decreased in the colon tissues of the Model+LV-SVCT1+QUE group(all P＜0.05).Conclusions SVCT1 can ameliorate oxidative stress and inflammatory response in the colon tissues of UC mice,and its mechanism may be related to the down-regulation of IL-1β,IL-6,TNF-α,MDA and ROS levels,as well as the up-regulation of NO and SOD expression.