长沙市第四医院(湖南师范大学附属长沙医院)内分泌科;
目的 探究糖原合成酶激酶-3β(GSK-3β)/环磷腺苷效应元件结合蛋白(CREB)信号通路调控巨噬细胞焦亡在糖尿病足溃疡(DFU)发生与发展中的作用及可能机制。方法 将30只大鼠随机分为：对照组、 DFU组及抑制GSK-3β组，每组10只。使用动态血糖检测仪检测大鼠空腹血糖(FBG)。观察记录各组大鼠创面愈合情况。HE染色检测创面组织病理变化。Masson染色检测创面组织纤维化水平。Western blot法检测创面组织中GSK-3β、 CREB、焦亡蛋白E(GSDME)、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)蛋白水平。免疫荧光染色检测创面组织中F4/80与GSDME、NLRP3共表达情况。ELISA试剂盒检测大鼠血清白细胞介素1β(IL-1β)、 IL-18含量。结果 与对照组相比，DFU组大鼠FBG升高；与DFU组相比，抑制GSK-3β组大鼠FBG降低。抑制GSK-3β组大鼠伤口愈合率从第3天到第14天一直高于DFU组，第14天差异显著，因此，后续实验采用第14天的样本。与对照组相比，DFU组大鼠创面组织明显断裂受损，胶原沉积缺损，创面组织中GSK-3β、 CREB与细胞焦亡相关蛋白GSDME、 NLRP3表达增加，F4/80与GSDME,F4/80与NLRP3共表达增加，血清中IL-1β、 IL-18水平增加；与DFU组相比，抑制GSK-3β组大鼠创面大部分组织愈合，胶原在断裂处沉积增加，创面组织中GSK-3β、 CREB与GSDME、 NLRP3表达减少，F4/80与GSDME,F4/80与NLRP3共表达减少，血清IL-1β、 IL-18水平减少。结论 GSK-3β/CREB信号通路与巨噬细胞焦亡在DFU大鼠创面明显上调，抑制该通路可促进DFU愈合，并下调巨噬细胞焦亡水平。
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基本信息:
DOI：10.13423/j.cnki.cjcmi.009885
中图分类号:R587.2
引用信息:
[1]何皓,杨艳丽,张沥.GSK-3β/CREB信号通路调控巨噬细胞焦亡参与糖尿病足溃疡发生与发展的机制研究[J].细胞与分子免疫学杂志,2024,40(12):1083-1088.DOI:10.13423/j.cnki.cjcmi.009885.
基金信息:
湖南省卫生健康委科研计划项目(D202303066984)