Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways

作者全名："Lu, Gongbiao; Zhang, Cunxin; Li, Kang; Gao, Kai; Fu, Maoqing; Lyu, Chaoliang; Quan, Zhengxue"

作者地址："[Lu, Gongbiao; Quan, Zhengxue] Chongqing Med Univ, Affiliated Hosp 1, Dept Spine Surg, 1 Youyi Rd, Chongqing 400042, Peoples R China; [Lu, Gongbiao; Zhang, Cunxin; Li, Kang; Fu, Maoqing; Lyu, Chaoliang] Jining 1 Peoples Hosp, Dept Spine Surg, 6 Hlth Rd, Jining 272011, Peoples R China; [Gao, Kai] Jining 1 Peoples Hosp, Dept Orthoped, Jining 272011, Peoples R China"

通信作者："Quan, ZX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Spine Surg, 1 Youyi Rd, Chongqing 400042, Peoples R China.; Lyu, C (通讯作者)，Jining 1 Peoples Hosp, Dept Spine Surg, 6 Hlth Rd, Jining 272011, Peoples R China."

来源：JOURNAL OF INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001091347400001

JCR分区：Q2

影响因子：4.2

年份：2023

卷号：16

期号：　

开始页：4777

结束页：4791

文献类型：Article

关键词：sinomenine; intervertebral disc degeneration; nucleus pulposus cells; apoptosis; Nrf2; NF-kappa B

摘要："Purpose: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1 beta (IL-1 beta)induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD).Methods: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1 beta to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL1 beta. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1 beta. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques.Results: IL-1 beta significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-kappa B signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1 beta injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes.Conclusion: SN can prevent IL-1 beta-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-kappa B signaling pathway."

基金机构：Natural Science Foundation of Shandong Province [ZR2021LZY008]; Shandong Traditional Chinese Medicine Science and Technology Project [Q-2022025]; Jining City Key Research and Development Program Project [2020JKNS008]; Shandong Province Medical and Health Science and Technology Development Plan Project [202104070383]

基金资助正文："<STRONG> </STRONG>This research was funded by Natural Science Foundation of Shandong Province, grant number ZR2021LZY008; Shandong Traditional Chinese Medicine Science and Technology Project, grant number Q-2022025; Jining City Key Research and Development Program Project, grant number 2020JKNS008 and Shandong Province Medical and Health Science and Technology Development Plan Project, grant number 202104070383."