基于内质网应激PERK-CHOP信号通路探讨冬虫夏草对高糖诱导的足细胞凋亡的影响*

作者：李冰心1,2，许军英1,2，张雅茹1,2，周小兵1,2

单位：1.湖南省第二人民医院/湖南省脑科医院，湖南 长沙 410021； 2.湖南中医药大学临床医学院，湖南 长沙 410021

引用：引用：李冰心，许军英，张雅茹，周小兵.基于内质网应激PERK-CHOP信号通路探讨冬虫夏草对高糖诱导的足细胞凋亡的影响[J].中医药导报,2025,31(5):8-12.

DOI：10.13862/j.cn43-1446/r.2025.05.002

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摘要：

目的：基于内质网应激探讨冬虫夏草（CS）对高糖诱导的足细胞凋亡的影响。方法：体外培养小鼠足细胞，分为正常葡萄糖浓度组（NG组）、高糖组（HG组）、高糖+CS组（HG+CS组）及高糖+4-苯基丁酸（内质网应激抑制剂）组（HG+4-PBA组）。采用CCK-8法检测细胞活性，流式细胞术检测细胞凋亡；Western blotting法检测足细胞中葡萄糖调节蛋白78（GRP78）、蛋白激酶RNA样内质网激酶（PERK）、磷酸化PERK（p-PERK）、真核翻译起始因子2α（eIF2α）、磷酸化eIF2α（p-eIF2α）、C/EBP同源蛋白（CHOP）及半胱氨酸天冬氨酸蛋白酶-12（Caspase-12）蛋白表达水平。结果：HG组足细胞活力低于NG组（P<0.05），足细胞凋亡率高于NG组（P<0.05）；HG组足细胞GRP78、CHOP、Caspase-12蛋白相对表达量及p-PERK/PERK、p-eIF2α/eIF2α均高于NG组（P＜0.05）；HG+CS组及HG+4-PBA组足细胞活力高于HG组（P<0.05），足细胞凋亡率低于HG组（P<0.05）；HG+CS组及HG+4-PBA组足细胞GRP78、CHOP、Caspase-12蛋白相对表达量及p-PERK/PERK、p-eIF2α/eIF2α均低于HG组（P＜0.05）。结论：冬虫夏草可通过减轻高糖诱导的足细胞内质网应激，减轻高糖作用下的足细胞损伤及凋亡，其作用机制可能为调控PERK-CHOP信号通路。

关键词：糖尿病肾脏病；足细胞；冬虫夏草；内质网应激；PERK-CHOP信号通路

Abstract：

Objective: To explore the effect of Cordycepssinensis (CS) on high glucose induced podocyte apoptosis based on endoplasmic reticulum stress. Method: Mouse podocytes were cultured in vitro and divided into normal glucose group (NG group), high glucose group (HG group), high glucose+Cordycepssinensis group (HG+CS group), high glucose+4-phenylbutyric acid (endoplasmic reticulum stress inhibitor) group(HG+4-PBA group). Cell viability  was detected by CCK8 method and cell apoptosis was detected by flow cytometry. Western blotting was used to detect the expression levels of GRP78, PERK, p-PERK, eIF2α, p-eIF2α, CHOP and Caspase-12 proteins in podocytes. Results: The cell viability of podocytes in the HG group was lower than those in NG group (P<0.05), and the cell apoptosis of podocytes in the HG group was higher than those in the NG group (P<0.05); The relative protein expression levels of GRP78, CHOP, Caspase-12 and p-PERK/ PERK、p-eIF2α/eIF2α in podocytes of HG group were higher than those in the NG group(P<0.05); The cell viability of podocytes in the HG+CS group and HG+4-PBA gralp were higher than those in the HG group(P<0.05), and the cell apoptosis of podocytes in the HG+CS group and HG+4-PBA gralp were lower than those in the HG group (P<0.05); The relative protein expression levels of GRP78, CHOP, Caspase-12 and p-PERK/PERK、p-eIF2α/eIF2α in podocytes of HG+CS group and HG+4-PBA gralp were lower than those in the HG group(P<0.05). Conclusion: Cordycepssinensis could rednce podocyte endoplasmic reticulum stress, alleviate high glucose reduced podocyte injury and apoptosis, which might be realized through regulating the PERK-CHOP signaling pathway.

Key words：diabetic kidneydisease; podocytes; Cordycepssinensis; endoplasmic reticulum stress; PERK-CHOP signaling pathway

发布时间：2025-12-23

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