冬凌草甲素调节Ikk/NF-κB信号通路对腰椎间盘退变大鼠髓核细胞凋亡的影响OA
Impact of oridonin on nucleus pulposus cell apoptosis in rats with lumbar disc degeneration by regulating Ikk/NF-κB signaling pathway
目的:探讨冬凌草甲素(ORI)调节Ikk/NF-κB信号通路对腰椎间盘退变大鼠髓核细胞凋亡的影响.方法:通过D-半乳糖皮下注射方式建立腰椎间盘退变大鼠模型,将建模成功的大鼠随机分为模型组、ORI低剂量(ORI-L)组(5 mg/kg ORI)、ORI中剂量(ORI-M)组(10 mg/kg ORI)、ORI高剂量(ORI-H)组(20 mg/kg ORI)及ORI-H+Ikkβ激活剂-普罗斯左汀(Prostra-tin)组(20 mg/kg ORI+0.5 mg/kg Prostratin),并以注射等体积生理盐水的大鼠作为正常组,每组10只;干预结束后,ELISA检测各组大鼠血清中炎症因子IL-1β、IL-10、TNF-α水平;取大鼠腰部椎间盘组织,HE及番红O染色检测腰椎间盘组织病理学变化;TUNEL染色检测组织中髓核细胞凋亡变化;qRT-PCR检测组织中细胞外基质标志物MMP13、ADAMTS4 mRNA变化;Western blot检测p-Ikkβ、Ikkβ、NF-κB p65、p-IkB、IkB蛋白表达.结果:与正常组相比,模型组髓核皱缩或消失、纤维环有缝隙,大鼠血清中TNF-α、IL-1β水平、病理评分、髓核细胞凋亡率、腰椎间盘组织中MMP13、ADAMTS4 mRNA表达、p-Ikkβ/Ikkβ、NF-κB p65、p-IkB/IkB表达显著升高,IL-10水平显著降低(P<0.05);与模型组相比,ORI-L组、ORI-M组、ORI-H组病理损伤得到改善,各定量指标均相反表达(P<0.05);Prostratin逆转了ORI-H对上述指标的影响(P<0.05).结论:ORI通过抑制Ikk/NF-κB信号通路改善腰椎间盘退变大鼠髓核细胞凋亡.
Objective:To investigate the impact of oridonin(ORI)on apoptosis of nucleus pulposus cells in rats with lumbar disc degeneration by regulating the Ikk/NF-κB signaling pathway.Methods:Rat model of lumbar intervertebral disc degeneration was established by subcutaneous injection of D-neneneba galactose.The successfully prepared rats were randomly separated into model group,ORI-L group(5 mg/kg ORI),ORI-M group(10 mg/kg ORI),ORI-H group(20 mg/kg ORI)and ORI-H+Ikkβ activator Pros-tatin group(20 mg/kg ORI+0.5 mg/kg Prostatin)and rats injected with equal volume of physiological saline were as normal group,with 10 rats in each group;after the intervention,ELISA was applied to detect levels of inflammatory factors IL-1β,IL-10 and TNF-α in serum of rats in each group;lumbar intervertebral disc tissue of rats was taken,HE and safranine O staining were applied to detect pathological changes in lumbar intervertebral disc tissue;TUNEL staining was applied to detect changes in apoptosis of nucleus pulposus cells in tissues;qRT-PCR was applied to detect changes in extracellular matrix markers MMP13 and ADAMTS4 mRNA in tissues;Western blot was applied to detect expressions of p-Ikkβ,Ikkβ,NF-κB p65,p-IkB,IkB proteins.Results:Compared with normal group,model group showed shrinkage or disappearance of nucleus pulposus and gaps in fibrous ring,levels of TNF-α and IL-1β in rat serum,pathological score,apoptosis rate of nucleus pulposus cells,MMP13,ADAMTS4 mRNA expressions,p-Ikkβ/Ikkβ,NF-κB p65,p-IkB/IkB expressions in lumbar disc tissue were obviously increased,while level of IL-10 was obviously decreased(P<0.05);compared with model group,pathological damage in ORI-L,ORI-M and ORI-H groups improved,and the quantitative indexes were opposite(P<0.05);Prostratin reversed effect of ORI-H on the above indexes(P<0.05).Conclusion:ORI improves nucleus pulposus cell apoptosis in rats with lumbar disc degeneration by inhibiting Ikk/NF-κB signaling pathway.
陈志鹏;段波
武汉市中医医院针灸科,武汉 430000武汉市中医医院针灸科,武汉 430000
医药卫生
冬凌草甲素Ikk/NF-κB信号通路腰椎间盘退变髓核细胞
OridoninIkk/NF-κB signaling pathwayLumbar disc degenerationNucleus pulposus cells
《中国免疫学杂志》 2026 (6)
1403-1408,6
武汉市医学科研项目(WZ19C17).
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