Lao Zhaobai, Fang Xuliang, Shen Shuchao, Zhang Yuliang, Chen Xin, Zhang Helou, Bian Yishan, Zhou Chengcong, Bao Ronghua, Xu Taotao, Jin Hongting, Fu Fangda, Wu Chengliang, Hu Changfeng, Ruan Hongfeng
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People's Republic of China.
Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, People's Republic of China.
J Inflamm Res. 2024 Oct 25;17:7705-7719. doi: 10.2147/JIR.S486297. eCollection 2024.
Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/ mouse model, which effectively replicates human SLE manifestations.
The study utilized MRL/ mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.
MRL/ mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.
Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征为免疫系统失调和自身抗体产生，可导致全身各系统广泛的炎症和损伤。尽管SLE患者中背痛普遍存在，但SLE与椎间盘（IVD）退变（背痛的主要原因）之间的联系仍未得到充分理解。本研究使用能有效复制人类SLE表现的MRL/lpr小鼠模型，探讨SLE对IVD退变的影响。
本研究利用MRL/lpr小鼠研究SLE对IVD退变的影响。评估小鼠的典型SLE表型和IVD退变指标，包括IVD高度、IVD评分、组织完整性、细胞外基质降解以及IVD细胞凋亡。此外，研究还检测了髓核（NP）的焦亡和炎性细胞因子分泌。机制分析聚焦于抗氧化途径，特别是NRF2、HO-1、KEAP1的表达水平以及p65的磷酸化水平。
MRL/lpr小鼠表现出典型的SLE表型，并加剧了IVD退变，包括IVD高度降低、IVD评分降低、IVD组织明显受损、细胞外基质降解以及IVD细胞凋亡增加。值得注意的是，SLE刺激NP焦亡和炎性细胞因子过度分泌。机制分析表明，SLE的进展通过下调NRF2和HO-1表达、上调KEAP1以及增强p65的磷酸化水平来阻碍抗氧化途径。
我们的研究结果突出了SLE与IVD退变之间的机制联系，为减轻SLE患者的背痛提供了潜在的治疗靶点。
