系統(tǒng)性紅斑狼瘡的發(fā)病觸發(fā)髓核細(xì)胞熱下垂，加劇椎間盤退變

2024年10月，浙江中醫(yī)藥大學(xué)第一附屬醫(yī)院（浙江省中醫(yī)醫(yī)院）骨科創(chuàng)傷研究所；杭州富陽中醫(yī)骨科創(chuàng)傷醫(yī)院；浙江中醫(yī)藥大學(xué)第一附屬醫(yī)院（浙江省中醫(yī)醫(yī)院）骨科；浙江中醫(yī)藥大學(xué)基礎(chǔ)醫(yī)學(xué)院 (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;  Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China;College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China) Hongting Jin老師研究團(tuán)隊(duì)在《Journal of Inflammation Research》上發(fā)表論文：

“The Onset of Systemic Lupus Erythematosus Triggers Nucleus Pulposus Cell Pyroptosis to Exacerbate Intervertebral Disc Degeneration"

“系統(tǒng)性紅斑狼瘡的發(fā)病觸發(fā)髓核細(xì)胞熱下垂，加劇椎間盤退變"

Abstract：

Purpose

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/lpr mouse model, which effectively replicates human SLE manifestations.

Methods

The study utilized MRL/lpr 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.

Results

MRL/lpr 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.

Conclusion

Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.

摘要：

目的：

系統(tǒng)性紅斑狼瘡（SLE）是一種以免疫系統(tǒng)失調(diào)和自身抗體產(chǎn)生為特征的自身免疫性疾病，可引起全身各系統(tǒng)的廣泛炎癥和損傷。盡管SLE患者普遍存在背痛，但SLE與椎間盤退變（IVD）之間的聯(lián)系仍未充分了解，椎間盤退變是背痛的主要原因。本研究通過MRL/lpr小鼠模型探索SLE對IVD變性的影響，該模型有效地復(fù)制了人類SLE的表現(xiàn)。

方法：

本研究利用MRL/lpr小鼠研究SLE對IVD變性的影響。評估小鼠的典型SLE表型和IVD變性指標(biāo)，包括IVD高度、IVD評分、組織完整性、細(xì)胞外基質(zhì)降解和IVD細(xì)胞凋亡。此外，研究還檢測了髓核（NP）焦亡和炎癥細(xì)胞因子分泌。機(jī)制分析側(cè)重于抗氧化途徑，特別是NRF2、HO-1、KEAP1的表達(dá)水平和p65的磷酸化水平。

結(jié)果：

MRL/lpr小鼠表現(xiàn)出典型的SLE表型，IVD退化加劇，包括IVD高度降低、IVD評分降低、IVD組織損傷明顯、細(xì)胞外基質(zhì)降解和IVD細(xì)胞凋亡增加。值得注意的是，SLE刺激NP焦亡和炎性細(xì)胞因子的過量分泌。機(jī)制分析表明，SLE的進(jìn)展通過下調(diào)NRF2和HO-1的表達(dá)，上調(diào)KEAP1，提高p65的磷酸化水平，從而阻礙了抗氧化途徑。

結(jié)論：

我們的研究結(jié)果強(qiáng)調(diào)了SLE和IVD變性之間的機(jī)制聯(lián)系，提出了緩解SLE患者背痛的潛在治療靶點(diǎn)。

該論文中，Rat NP cell line (rNPCs)的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。