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。
Abstract
Objective To investigate the protective effects and mechanism of selenocsteine (Sec) and resveratrol (Res) on ulcerative colitis (UC) in mice. Methods Male C57BL/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 (0.9mg/kg) and Res (100mg/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.
关键词
白藜芦醇 /
硒代半胱氨酸 /
溃疡性结肠炎 /
RET磷酸化
Key words
resveratrol /
selenocysteine /
ulcerative colitis /
RET phosphorylation
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Le Berre C, Jairath V, Panaccione R, et al. Artificial intelligence for clinical trial facilitation, lessons for inflammatory bowel disease: a scoping review[J]. Clin Gastroenterol Hepatol, 2025, 23:2399–2422.
[2] Liang Y, Li Y, Lee C, et al. Ulcerative colitis: molecular insights and intervention therapy[J]. Mol Biomed, 2024, 5:42.
[3] Torres J, Halfvarson J, Rodríguez-Lago I, et al. Results of the seventh scientific workshop of ECCO: precision medicine in IBD—prediction and prevention of inflammatory bowel disease[J]. J Crohns Colitis, 2021, 15:1443–1454.
[4] Hansebout CR, Su C, Reddy K, et al. Enteric glia mediate neuronal outgrowth through release of neurotrophic factors[J]. Neural Regen Res, 2012, 7:2165–2175.
[5] Schreiber S, Fedorak RN, Nielsen OH, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's disease IL-10 cooperative study group[J]. Gastroenterology, 2000, 119:1461–1472.
[6] Xiao W, Wang W, Chen W, et al. GDNF is involved in the barrier-inducing effect of enteric glial cells on intestinal epithelial cells under acute ischemia reperfusion stimulation[J]. Mol Neurobiol, 2014, 50:274–289.
[7] Kawai K, Takahashi M.Intracellular RET signaling pathways activated by GDNF[J]. Cell Tissue Res, 2020, 382:113–123.
[8] Han M, Liu K.Selenium and selenoproteins: their function and development of selenium-rich foods[J]. Int J Food Sci Technol, 2022, 57:7026–7037.
[9] Lee JM, Chun HJ, Choi HS, et al. Selenium administration attenuates 5-flurouracil-induced intestinal mucositis
[J]. Nutr Cancer, 2017, 69:616–622.
[10] Yang CC, Yao CA, Lin YR, et al. Deep-sea water containing selenium provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1[J]. PLoS One, 2014, 9:e96006.
[11] Kitada M, Koya D.Renal protective effects of resveratrol[J]. Oxid Med Cell Longev, 2013, 2013:568093.
[12] Filardo S, Di Pietro M, Mastromarino P, et al. Therapeutic potential of resveratrol against emerging respiratory viral infections[J]. Pharmacol Ther, 2020, 214:107613.
[13] Saez A, Gomez-Bris R, Herrero-Fernandez B, et al. Innate lymphoid cells in intestinal homeostasis and inflammatory bowel disease[J]. Int J Mol Sci, 2021, 22:7618.
[14] Zhang L, Xue H, Zhao G, et al. Curcumin and resveratrol suppress dextran sulfate sodium-induced colitis in mice[J]. Mol Med Rep, 2019, 19:3053–3060.
[15] Yu B, Wang Y, Tan Z, et al. Resveratrol ameliorates DSS-induced ulcerative colitis by acting on mouse gut microbiota[J]. Inflammopharmacology, 2024,32:2023–2033.
[16] Shi C, Yue F, Shi F, et al. Selenium-containing amino acids protect dextran sulfate sodium-induced colitis via ameliorating oxidative stress and intestinal inflammation[J]. J Inflamm Res,2021,14:85-95.
[17] Zhao M, Xie B, Li Y, et al. Resveratrol prevents gallstones in mice fed on a high fat diet via regulating PPAR-γ and SR-BI[J]. Front Pharmacol,2025, 16:1543865.
[18] Ghia JE, Blennerhassett P, Collins SM.Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression[J]. J Clin Invest, 2008, 118:2209–2218.
[19] Guo H, Guo H, Xie Y, et al. Mo3Se4 nanoparticle with ROS scavenging and multi-enzyme activity for the treatment of DSS-induced colitis in mice[J]. Redox Biol, 2022, 56:102441.
[20] Yarani R, Mirza AH, Kaur S, et al. The emerging role of lncRNAs in inflammatory bowel disease[J]. Exp Mol Med, 2018, 50:1–14.
[21] 于馨雅. 基于Nrf2/HO-1通路研究白藜芦醇对溃疡性结肠炎肠黏膜炎症反应及屏障损伤的保护作用[D]. 大理:大理大学, 2024.
[22] Pan HH, Zhou XX, Ma YY, et al. Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy[J]. World J Gastroenterol, 2020, 26: 4945–4959.
[23] Kaushal N, Kudva AK, Patterson AD, et al. Crucial role of macrophage selenoproteins in experimental colitis[J]. J Immunol, 2014, 193:3683-3692.
[24] Ooi CJ, Hilmi I, Banerjee R, et al. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia[J]. J Gastroenterol Hepatol, 2019, 34:1296–1315.
[25] Progatzky F, Shapiro M, Chng SH, et al. Regulation of intestinal immunity and tissue repair by enteric glia[J]. Nature,2021, 599:125-130.
[26] Lu S, Xu Y, Zhang H, et al. Glycyrol Relieves Ulcerative Colitis by Promoting the Fusion of ZO-1 with the Cell Membrane through the Enteric Glial Cells GDNF/RET Pathway[J]. J Agric Food Chem,2024, 72:14653-14662.
[27] Kawai K, Takahashi M.Intracellular RET signaling pathways activated by GDNF[J].Cell Tissue Res,2020, 382:113-123.
基金
国家自然科学基金青年项目（No.82304147）
PDF(6978 KB)
