【摘要】 目的 探究硒代半胱氨酸（selenocysteine,Sec）和白藜芦醇（resveratrol,Res）对溃疡性结肠炎(ulcerative colitis,UC)小鼠保护作用及其作用机制。方法 雄性C57BL/6J小鼠随机分为对照组（control,CON）、UC模型组（model,M）、Sec干预组、Res干预组，每组8只，进行为期14 d的干预实验。CON组饮用蒸馏水；M组、Sec组和Res组正常喂养3 d后用2.5%葡聚糖硫酸钠(dextran sulfate sodium,DSS）干预7 d，之后饮用蒸馏水恢复4 d；同时，Sec组和Res组从实验第1 d开始灌胃Sec(0.9 mg/kg)和Res(100 mg/kg)，持续14 d，其他组灌胃生理盐水；四组均正常饮食。实验结束后，通过分析体重、摄食量、结肠长度、DAI评分和组织病理学变化评估Sec和Res对UC的防护效果；通过Western blot检测小鼠结肠组织中p-RET的表达水平，并通过相关分析，判断Sec和Res缓解UC是否与调控RET磷酸化有关。结果 与CON组相比，M组体重、结肠长度显著降低（P<0.05）,DAI评分较显著升高（P<0.05），可见大量隐窝缺失和炎性浸润等组织病理损伤, p-RET蛋白水平显著降低（P<0.05）；与M组相比，Res显著改善UC小鼠的结肠长度、DAI以及结肠组织病理损伤，降低组织病理学评分并增加结肠组织中p-RET蛋白表达（P<0.05）；而Sec有一定保护效果，但部分指标差异无统计学意义。相关性分析结果显示，结肠长度与p-RET蛋白表达呈正相关关系，而DAI和组织病理学评分与p-RET蛋白表达呈负相关关系。结论 Res和Sec可改善UC，且Res效果更佳，其作用机制可能与上调RET的磷酸化水平有关。更多还原

【Abstract】 Objective To investigate the protective effects and mechanism of selenocsteine(Sec) and resveratrol(Res) on ulcerative colitis(UC) in mice. Methods Male C57 BL/6J mice were randomly divided into control group(CON), UC model group(M), Sec intervention group, and Res intervention group, with 8 mice in each group. A 14-day intervention experiment was conducted. The CON group drank distilled water normally, and distilled water was changed every two days. The M group, Sec group and Res group were treated with 2.5% dextran sulfate sodium(DSS)for 7 days after normal feeding for 3 days, followed by drinking distilled water for 4 days. At the same time, the Sec group and the Res group were given by gavage with Sec(0.9 mg/kg) and Res(100 mg/kg) for 14 days from the first day of the experiment, and the other groups were given saline. Finally, the mice were euthanized. The protective effect of Sec and Res on UC was evaluated by analyzing body weight, food intake, colon length, DAI score and histopathological changes. The expression level of p-RET in colon tissue was detected by Western blot, and Pearson correlation analysis was performed to investigate the relationship between the changes of UC parameters and RET phosphorylation after Sec and Res intervention. Results Compared with the CON group, the body weight and colon length of the M group were significantly reduced(P<0.05), the DAI score was significantly increased(P<0.05), and remarkable histopathological damages such as crypt deletion and inflammatory infiltrates were observed, and the level of p-RET protein was significantly reduced(P<0.05). Compared with the M group, the Res group significantly improved the colon length, DAI, and the pathological damage of colon tissue. The histopathological score was reduced and the expression of p-RET protein in the colon tissue was increased(P<0.05). The Sec group had a certain protective effect, but there was no significant difference in some parameters. The results of Pearson correlation analysis showed that colon length was positively correlated with p-RET protein expression, while DAI and histopathology score were negatively correlated with p-RET protein expression. Conclusion Both Res and Sec can improve UC, and Res has a better effect. Its mechanism is related to the upregulation of the phosphorylation level of RET.更多还原