中国麻风皮肤病杂志 ›› 2023, Vol. 39 ›› Issue (12): 868-873.doi: 10.12144/zgmfskin202312868

• 论著 • 上一篇    下一篇

Hypocrellin A通过ROS/JNK通路促进瘢痕疙瘩成纤维细胞凋亡的作用及机制

陈雷刚1,任慧敏1,吴远慧1,安国芝1,景晓蕾2,赵同心2   

  1. 1河北北方学院附属第一医院，河北省张家口市，075000；2河北北方学院，河北省张家口市，075051
  • 出版日期:2023-12-15 发布日期:2023-11-21

The effect and mechanism of Hypocrellin A promotes apoptosis of Keloid fibroblasts through ROS/JNK pathway

CHEN Leigang1, REN Huimin1, WU Yuanhui1, AN Guozhi1, JING Xiaolei2, ZHAO Tongxin2   

  1. 1 The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China; 2 Hebei North University, Zhangjiakou 075051, China
  • Online:2023-12-15 Published:2023-11-21

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摘要： 目的：探索Hypocrellin A（HA）通过活性氧簇（ROS）/ c-Jun氨基末端激酶（JNK）通路促进瘢痕疙瘩成纤维细胞凋亡的作用及机制。方法：原代培养KFs并进行传代，第3代KFs分为对照组、不同剂量HA组（0.125、0.25、0.5、1.0 μmol/L HA处理）、HA+乙酰半胱氨酸（NAC）组（1.0 μmol/L HA+1.0 mmol/L NAC处理）。检测细胞增殖的光密度OD450，凋亡率，胶原代谢指标I型胶原（Col-I）、α-平滑肌肌动蛋白（α-SMA）、纤维连接蛋白（FN）、氧化应激指标丙二醛（MDA）、超氧化物歧化酶（SOD）、总抗氧化力（T-AOC）及ROS的含量，内质网应激标志物GRP78、p-IRE-1及ROS/JNK通路中p-JNK、cleaved caspase-3的表达水平。结果：不同剂量HA组的OD450、Col-I、α-SMA、FN、SOD、T-AOC的含量均低于对照组，凋亡率、MDA、ROS含量及GRP78、p-IRE-1、p-JNK、cleaved caspase-3的表达水平均高于对照组（P<0.05）且HA剂量越高，上述指标的变化越显著；HA+NAC组的OD450、Col-I、α-SMA、FN、SOD、T-AOC的含量均高于1.0 μmol/L HA组，凋亡率、MDA、ROS含量及GRP78、p-IRE-1、p-JNK、cleaved caspase-3的表达水平均低于1.0 μmol/L HA（P<0.05）。结论：HA通过促进KFs凋亡，这一作用与激活ROS/JNK通路介导的氧化应激和内质网应激有关。

关键词: 瘢痕疙瘩, 成纤维细胞, Hypocrellin A, 凋亡, 活性氧簇, c-Jun氨基末端激酶

Abstract: Objective: To explore the role and mechanism of Hypocrellin A (HA) in promoting apoptosis of Keloid fibroblasts (KFs) through reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway. Methods: KFs were primarily cultured and passaged. The 3rd generation KFs were divided into control group and different dose HA groups (0.125, 0.25, 0.5, 1.0 μmol/L HA treatment), HA+N-acetylcysteine (NAC) group (1.0 μmol/L HA+1.0 mmol/L NAC treatment). The optical density OD450 of cell proliferation, apoptosis rate, the contents of collagen metabolism indicators type I collagen (Col-I), α-smooth muscle actin(α-SMA), fibronectin (FN), oxidative stress indicators malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and ROS, and the expression levels of endoplasmic reticulum stress markers GRP78, p-IRE-1 and p-JNK, cleaved caspase-3 in the ROS/JNK pathway were detected. Results: The OD450 level, the contents of Col-I α-SMA, FN, SOD, T-AOC in the control group were lower than those in the control group, while the apoptosis rate, the contents of MDA, ROS, and the expression levels of GRP78, p-IRE-1, p-JNK and cleared caspase-3 were higher than those in the control group (P<0.05). The higher the HA dose, the more significant the changes in the above indicators. The OD450 level, the contents of Col-I α-SMA, FN, SOD, T-AOC in the control group were lower than those in the HA+NAC group were higher than those in the 1.0 μmol/L HA group, while the apoptosis rate, the contents of MDA, ROS, and the expression levels of GRP78, p-IRE-1, p-JNK and cleared caspase-3 were lower than those in the 1.0 μmol/L HA group (P<0.05). Conclusion: HA promotes the apoptosis of KFs, which is related to the activation of ROS/JNK pathway mediated oxidative stress and endoplasmic reticulum stress.

Key words: keloid, fibroblasts, Hypocrellin A, apoptosis, reactive oxygen species, c-Jun N-terminal kinase