壮骨活血汤介导内质网应激调控人软骨细胞凋亡防治膝关节骨性关节炎的机制

Mechanism of Zhuanggu Huoxue Decoction mediating endoplasmic reticulum stress and regulating chondrocyte apoptosis to prevent knee osteoarthritis

目的:探讨壮骨活血汤抑制内质网应激(ERS)介导的人软骨细胞凋亡防治膝关节骨性关节炎(KOA)的机制。方法:采用人软骨细胞制作ERS模型,分为对照组、衣霉素组、衣霉素+4-PBA组、衣霉素+含药血清组,检测细胞凋亡、炎症因子和炎症相关通路蛋白激酶B(AKT)与核因子κB(NF-κB)活化情况,探索ERS调控的凋亡相关信号通路活化情况。结果:衣霉素可以明显诱导人软骨细胞凋亡,而壮骨活血汤含药血清可以抑制衣霉素的促凋亡作用(P<0.05)。衣霉素+含药血清组中白细胞介素-1β(IL-1β)及肿瘤坏死因子-α(TNF-α)表达显著低于衣霉素组(P<0.05)。壮骨活血汤含药血清能减轻衣霉素诱导的炎症相关通路的活化,并且可以明显抑制ERS相关凋亡通路活化。结论:壮骨活血汤可能通过抑制ERS相关凋亡通路活化降低人软骨细胞凋亡,进而发挥治疗KOA的作用。

Objective:To investigate the mechanism of Zhuanggu Huoxue Decoction in preventing and treating knee osteoarthritis(KOA) by inhibiting endoplasmic reticulum stress(ERS) mediated human chondrocyte apoptosis.Methods:Human chondrocytes were used to make ERS model.The cells were divided into control group,tunicamycin group,tunicamycin+4-PBA group and tunicamycin+drug-containing serum group.The apoptosis,inflammatory factors and activation of inflammation-related pathways of protein kinase B(AKT) and nuclear factor kappa B(NF-κB) were detected.In addition we explored the activation of apoptosis-related signaling pathways regulated by ERS.Results:The apoptosis of human chondrocytes could be induced obviously by tunicamycin.The drug-containing serum of Zhuanggu Huoxue Decoction can inhibit the apoptosis-promoting effect(P<0.05).The level of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in tunicamycin+drug-containing serum group were significantly lower than those in tunicamycin group(P<0.05).The drug-containing serum of Zhuanggu Huoxue Decoction could significantly inhibit the activation of inflammatory pathways and ERS-related apoptotic pathway induced by tunicamycin.Conclusion:Zhuanggu Huoxue Decoction may play a role in the treatment of KOA by reducing apoptosis in human chondrocytes through inhibition of activation of ERS-related apoptotic pathways.