摘　要：为研究雷帕霉素对高糖诱导的足细胞损伤及相关机制，体外培养人肾小球足细胞（HGPC），将细胞分为对照组、模型组、雷帕霉素组、抑制剂组、雷帕霉素+抑制剂组及雷帕霉素+激活剂组，观察足细胞形态、肿瘤坏死因子-α（TNF-α）及白介素-1β（IL-1β）的表达水平、细胞增殖率及凋亡率，以及NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、半胱氨酸天门冬氨酸蛋白酶-1（Caspase-1）的mRNA和蛋白质及p38丝裂原活化蛋白激酶（p38 MAPK）通路关键蛋白的表达水平。与对照组相比，模型组可见细胞排列疏松、间隔增大、增殖率降低（P<0.05），TNF-α及IL-1β的表达水平、凋亡率以及NLRP3、ASC、Caspase-1 的mRNA和蛋白质及p-p38 MAPK的蛋白质的表达水平升高（P<0.05）；与模型组相比，雷帕霉素组和抑制剂组中上述细胞状态和指标得到改善（P<0.05）；与雷帕霉素组相比，雷帕霉素+抑制剂组中上述细胞状态和指标进一步得到改善（P<0.05），而雷帕霉素+激活剂组中的表现则相反（P<0.05）。雷帕霉素可通过抑制p38 MAPK信号通路改善高糖诱导的足细胞形态，促进细胞增殖，抑制细胞凋亡、炎症释放及NLRP3炎性小体激活。这为糖尿病肾病的研究提供了参考依据。
关键词：糖尿病肾病；足细胞；雷帕霉素；NOD样受体蛋白3炎症小体；p38丝裂原活化蛋白激酶
中图分类号：R587.1；R977.9　　　　文献标志码：A　　　　DOI：10.3969/j.issn.1007-7146.2025.02.010

Abstract: To investigate rapamycin’s effect on high-glucose induced podocyte injury and its related mechanism, human glomerular podocytes (HGPC) were cultured in vitro. The cells were divided into control group, model group, rapamycin group, inhibitor group, rapamycin + inhibitor group and rapamycin + activator group. Podocyte morphology, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, cell proliferation rate, apoptosis rate, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate protease-1 (Caspase-1) mRNA, protein and p38 mitogen-activated protein kinase (p38 MAPK) pathway key protein expression levels were observed. Compared with the control group, the cell arrangement was loose, the cell septum increased, and the cell proliferation rate decreased in the model group (P<0.05), and the levels of TNF-α and IL-1β, apoptosis rate, NLRP3, ASC, Caspase-1 mRNA and protein, and p-p38 MAPK protein increased (P<0.05). Compared with model group, the above cell states and indexes were improved in rapamycin group and inhibitor group (P<0.05). Compared with the rapamycin group, the above cell status and indexes were further improved in the rapamycin + inhibitor group (P<0.05), whereas the opposite was observed in the rapamycin + activator group (P<0.05). Rapamycin can improve the morphology of high glucose induced podiocytes by inhibiting p38 MAPK signaling pathway, promote cell proliferation, inhibit cell apoptosis, inflammatory release and activation of NLRP3 inflammasome, could provide reference for the study of diabetic nephropathy.
Key words: diabetic nephropathy; podocyte; rapamycin; NOD-like receptor protein 3 inflammasome; p38 mitogen-activated protein kinase
（Acta Laser Biology Sinica, 2025, 34(2): 176-183）