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目的 探讨miR-155-5p/沉默信息调节因子1(sirt1)信号通路对白色念珠菌诱导川崎病模型小鼠免疫功能的影响。方法 将C56BL/6小鼠分为对照组、川崎病组、拮抗剂对照组、miR-155-5p拮抗剂组、miR-155-5p拮抗剂+si-NC组、miR-155-5p拮抗剂+si-sirt1组，每组12只。除对照组外，其他组小鼠均通过腹腔注射白色念珠菌水溶物构建川崎病模型。建模成功后进行给药处理，1 d给药1次，持续7 d。qRT-PCR检测冠状动脉中miR-155-5p表达；Western blot检测冠状动脉中sirt1蛋白；HE染色检测冠状动脉的病理变化；检测小鼠胸腺指数和脾指数；流式细胞术检测外周血中辅助性T细胞17(Th17)/调节性T细胞(Treg);ELISA检测小鼠血清中白细胞介素(IL)-17、IL-10水平；验证sirt1与miR-155-5p靶向关系。结果 与对照组比较，川崎病组小鼠冠状动脉中有大量炎性细胞浸润，miR-155-5p表达、Th17比例、Th17/Treg比例、IL-17水平升高，sirt1蛋白表达、胸腺指数、脾指数、Treg比例、IL-10水平降低(均P<0.05);与川崎病组比较，miR-155-5p拮抗剂组小鼠冠状动脉中炎性细胞浸润现象有所缓解，miR-155-5p表达、Th17比例、Th17/Treg比例、IL-17水平降低，sirt1蛋白表达、胸腺指数、脾指数、Treg比例、IL-10水平升高(均P<0.05);si-sirt1减弱了抑制miR-155-5p对川崎病小鼠Th17/Treg平衡的促进作用以及对血管炎症的抑制作用，miR-155-5p靶向调控sirt1。结论 抑制miR-155-5p促进川崎病小鼠Th17/Treg平衡，抑制血管炎症的机制可能与上调sirt1表达有关。
Abstract：Objective To investigate the effect of the miR-155-5p/silent information regulator 1(sirt1) signaling pathway on the immune function of Candida albicans induced Kawasaki disease model mice. Methods C56BL/6 mice were separated into control group, Kawasaki disease group, antagonist control group, miR-155-5p antagonist group, miR-155-5p antagonist+si-NC group, and miR-155-5p antagonist+si-sirt1 group, with 12 mice in each group. Except for the control group, mice in all other groups were used to construct a Kawasaki disease model by intraperitoneal injection of water-soluble Candida albicans. After successful modeling, administration was performed once a day for 7 days. QRT-PCR was applied to detect the expression of miR-155-5p in coronary arteries. Western blot was applied to detect sirt1 protein in coronary arteries. HE staining was applied to detect pathological changes in coronary arteries. Mouse thymus index and spleen index were detected. Flow cytometry was applied to detect helper T cells 17(Th17)/regulatory T cells(Treg) in peripheral blood. ELISA was applied to detect the levels of interleukin(IL)-17 and IL-10 in mouse serum. The targeting relationship between sirt1 and miR-155-5p was validated. Results Compared with the control group, there was a large amount of inflammatory cell infiltration in the coronary arteries of mice in the Kawasaki disease group. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level increased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level decreased(P<0.05). Compared with the Kawasaki disease group, the inflammatory cell infiltration in the coronary arteries of mice in the miR-155-5p antagonist group was alleviated. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level decreased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level increased(P<0.05). Si-sirt1 weakened the promoting effect of miR-155-5p inhibition on Th17/Treg balance and the inhibitory effect on vascular inflammation in Kawasaki disease mice, miR-155-5p targeted and regulated sirt1. Conclusion The mechanism by which inhibiting miR-155-5p promotes Th17/Treg balance and inhibits vascular inflammation in Kawasaki disease mice may be related to the upregulation of sirt1 expression.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.02.017
中图分类号:R725.4;R-332
引用信息:
[1]魏刚,田晶,梁冬雪等.miR-155-5p/sirt1信号通路对白色念珠菌诱导川崎病模型小鼠免疫功能的影响[J].安徽医科大学学报,2025,60(02):307-312+320.DOI:10.19405/j.cnki.issn1000-1492.2025.02.017.
基金信息:
辽宁省教育厅基本科研面上项目(编号：LJKMZ20221229)~~