【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、1.0μmol/L HA处理)、HA+乙酰半胱氨酸(NAC)组(1.0μmol/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1.0μmol/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1.0μmol/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。更多还原

【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.更多还原