蓝萼甲素调节PINK1/Parkin信号通路对IL-1β诱导的关节软骨细胞自噬和凋亡的影响

doi:10.3969/j.issn.1006-6233.2024.08.03

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摘要 目的: 探讨蓝萼甲素(GLA)调节PTEN诱导的激酶1(PINK1)/E3泛素连接酶(Parkin)信号通路对白细胞介素1β(IL-1β)诱导的关节软骨细胞自噬和凋亡的影响。方法: 将关节软骨细胞分为Control组、IL-1β组、L-GLA组、M-GLA组、H-GLA组、Suramin组;细胞计数试剂盒8(CCK8)法检测关节软骨细胞增殖;TEM检测关节软骨细胞自噬;流式细胞仪检测关节软骨细胞凋亡;ELISA检测关节软骨细胞中炎性因子(MMP3、TNF-α、MMP13)和活性氧(ROS)水平;蛋白印迹法检测关节软骨细胞中裂解的胱天蛋白酶3(cleaved caspase-3)、微管相关蛋白1轻链3(LC3)I、LC3Ⅱ、P62、PINK1、Parkin蛋白表达。结果: 与Control组相比,IL-1β组存活率、LC3Ⅱ/Ⅰ、PINK1、Parkin降低,自噬空泡数、凋亡率、MMP3、TNF-α、MMP13、ROS、cleaved caspase-3、P62升高(P<0.05);L-GLA组、M-GLA组、H-GLA组存活率、自噬空泡数、LC3Ⅱ/Ⅰ、PINK1、Parkin高于IL-1β组,凋亡率、MMP3、TNF-α、MMP13、ROS、cleaved caspase-3、P62低于IL-1β组(P<0.05);Suramin组存活率、自噬空泡数、LC3Ⅱ/Ⅰ、PINK1、Parkin低于H-GLA组,凋亡率、MMP3、TNF-α、MMP13、ROS、cleaved caspase-3、P62高于H-GLA组(P<0.05)。结论: GLA通过激活IL-1β诱导的关节软骨细胞自噬,抑制细胞凋亡,进而抑制OA的进展,其机制可能是通过激活PINK1/Parkin信号通路实现的。

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	高翔
	李巍
	陈何

关键词 ：蓝萼甲素, PTEN诱导的激酶1, E3泛素连接酶, IL-1β, 关节软骨细胞, 自噬, 凋亡

Abstract：Objective: To investigate the effect of geniposide (GLA) on PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) signaling pathway in regulating autophagy and apoptosis of articular chondrocytes induced by interleukin-1β (IL-1β).Methods: Articular chondrocytes were divided into Control, IL-1β, Low-GLA, Medium-GLA, High-GLA, and Suramin groups. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK8) assay. Autophagy was detected by transmission electron microscopy (TEM). Apoptosis was measured by flow cytometry. Levels of inflammatory factors (MMP3, TNF-α, MMP13) and reactive oxygen species (ROS) in chondrocytes were detected by ELISA. Protein expressions of cleaved caspase-3, microtubule-associated protein 1 light chain 3 (LC3) I, LC3II, P62, PINK1, and Parkin were analyzed by Western blot.Results: Compared with the Control group, the IL-1β group showed decreased cell viability, LC3II/I ratio, PINK1, and Parkin, while autophagic vacuole number, apoptosis rate, MMP3, TNF-α, MMP13, ROS, cleaved caspase-3, and P62 were increased (P<0.05). The Low-GLA, Medium-GLA, and High-GLA groups exhibited higher cell viability, autophagic vacuole number, LC3II/I ratio, PINK1, and Parkin than the IL-1β group, with lower apoptosis rate, MMP3, TNF-α, MMP13, ROS, cleaved caspase-3, and P62 (P<0.05). The Suramin group showed lower cell viability, autophagic vacuole number, LC3II/I ratio, PINK1, and Parkin than the High-GLA group, with higher apoptosis rate, MMP3, TNF-α, MMP13, ROS, cleaved caspase-3, and P62 (P<0.05).Conclusion: GLA inhibits the progression of osteoarthritis (OA) by activating autophagy and inhibiting apoptosis in IL-1β-induced articular chondrocytes, possibly through the activation of the PINK1/Parkin signaling pathway.

Key words： Glaucocalyxin A PTEN-induced kinase 1 E3 ubiquitin ligase IL-1β Articular chondrocytes Autophagy Apoptosis

基金资助:四川省卫生健康委员会科研课题,(编号:19PJ100)

引用本文:

高翔, 李巍, 陈何. 蓝萼甲素调节PINK1/Parkin信号通路对IL-1β诱导的关节软骨细胞自噬和凋亡的影响[J]. 河北医学, 2024, 30(8): 1244-1249.
GAO Xiang, LI Wei, CHEN He. Effects of GLA on IL-1β-Induced Autophagy and Apoptosis in Articular Chondrocytes via PINK1/Parkin Pathway. HeBei Med, 2024, 30(8): 1244-1249.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.08.03 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I8/1244

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