Yao Sai, Li Yanan, Ruan Hongfeng, Wu Lianguo, Zeng Hanbing
Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People's Republic of China.
Frontier Innovation Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China.
J Inflamm Res. 2025 Apr 18;18:5293-5309. doi: 10.2147/JIR.S492365. eCollection 2025.
Intervertebral disc (IVD) degeneration (IVDD) is highly prevalent among the elderly population and stands as a leading cause of low back pain. Our prior studies have highlighted the therapeutic potential of Gubi decoction (GBD) in alleviating knee osteoarthritis, however, but the specific mechanism of GBD in treating IVDD is not clear.
To ascertain the clear mechanism of GBD for enhancing its therapeutic efficacy in treating lVDD, through comparison of its effects across different doses of GBD and clinical positive control drugs using a mouse IVDD model.
In this study, 8-week-old male mice were treated with lumbar spine instability (LSI) surgery to construct IVDD model mice. From day 3 post-LSI surgery, mice in the loxoprofen sodium tablets (LST), GBD-L, GBD-M and GBD-H groups were gavage administration with LST (23.1 mg/kg) and GBD (6.1, 12.2 and 24.4 g/kg body weight, respectively) 5 times a week for 4 and 8 weeks separately. After 8 weeks of LSI modeling, the therapeutic efficacy on IVDD was evaluated through changes in lumbar spine function, histopathological morphology, extracellular matrix (ECM) metabolism, nucleus pulposus (NP) cell viability, and cartilage endplate (CEP) cell pyroptosis; at 4 weeks after modeling, the activation of NF-κB signaling was detected.
GBD can attenuate the progression of IVDD in mice, resulting in substantially increases disc height index (DHI) and NP matrix, reduced the degree of annulus fibrosus (AF) tear and the formation of cavity in CEP. In parallel, GBD significantly improved the matrix metabolism-related indexes of IVD at 8 weeks after modeling. Mechanically, GBD inhibited the expression of pyroptosis-related indicators NOD-like receptor thermal protein-domain associated protein 3 (NLRP3), cysteinyl aspartate specific-proteinase-1 (CASPASE1), gasdermin D (GSDMD), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in CEP. Furthermore, GBD suppressed nuclear translocation of P65 protein, and decreased the amount of p-I-κB in CEP at 4 weeks after modeling.
In summary, GBD can effectively inhibit the activation of NF-κB signaling and pyroptosis of ECP, relieve the porosity of ECP, and then delay the IVDD process. GBD may serve as a potential therapeutic agent for IVDD treatment.
椎间盘退变（IVDD）在老年人群中极为普遍，是腰痛的主要原因。然而，我们之前的研究强调了骨痹汤（GBD）在缓解膝关节骨关节炎方面的治疗潜力，但GBD治疗IVDD的具体机制尚不清楚。
通过使用小鼠IVDD模型比较不同剂量GBD与临床阳性对照药物的效果，以确定GBD增强其治疗IVDD疗效的明确机制。
在本研究中，对8周龄雄性小鼠进行腰椎不稳（LSI）手术以构建IVDD模型小鼠。自LSI手术后第3天起，洛索洛芬钠片（LST）组、GBD-L组、GBD-M组和GBD-H组小鼠分别每周5次灌胃给予LST（23.1mg/kg）和GBD（分别为6.1、12.2和24.4g/kg体重），持续4周和8周。在LSI建模8周后，通过腰椎功能、组织病理学形态、细胞外基质（ECM）代谢、髓核（NP）细胞活力和软骨终板（CEP）细胞焦亡的变化评估对IVDD的治疗效果；在建模4周后，检测NF-κB信号的激活情况。
GBD可减轻小鼠IVDD的进展，导致椎间盘高度指数（DHI）和NP基质显著增加，纤维环（AF）撕裂程度降低以及CEP中腔隙形成减少。同时，GBD在建模8周后显著改善了IVD的基质代谢相关指标。机制上，GBD抑制了CEP中焦亡相关指标NOD样受体热蛋白结构域相关蛋白3（NLRP3）、半胱天冬酶-1（CASPASE1）、gasdermin D（GSDMD）、白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的表达。此外，GBD在建模4周后抑制了P65蛋白的核转位，并降低了CEP中p-I-κB的含量。
综上所述，GBD可有效抑制NF-κB信号的激活和ECP的焦亡，减轻ECP的孔隙率，进而延缓IVDD进程。GBD可能成为治疗IVDD的潜在治疗药物。
