[1]颜珍珍 李媛媛 郭冉 赵天才 谢洋 刘涛 任志鑫 袁宇飞 苗洁 张存.维生素D在椎间盘退变中的作用及机制研究[J].中国中医骨伤科杂志,2026,34(05):10-17.[doi:10.20085/j.cnki.issn1005-0205.260502]
　YAN Zhenzhen,LI Yuanyuan,GUO Ran,et al.The Role and Mechanism of Vitamin D in Intervertebral Disc Degeneration[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(05):10-17.[doi:10.20085/j.cnki.issn1005-0205.260502]
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维生素D在椎间盘退变中的作用及机制研究()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年05期
页码:
10-17
栏目:
基础研究
出版日期:
2026-05-10

文章信息/Info

Title:
The Role and Mechanism of Vitamin D in Intervertebral Disc Degeneration
文章编号:
1005-0205(2026)05-0010-08
作者:
颜珍珍 李媛媛 郭冉 赵天才 谢洋 刘涛 任志鑫 袁宇飞 苗洁 张存
1邯郸市中心医院(河北 邯郸,056001)
Author(s):
YAN Zhenzhen1; LI Yuanyuan1; GUO Ran1; ZHAO Tiancai1; XIE Yang1; LIU Tao1; REN Zhixin1; YUAN Yufei1; MIAO Jie1; ZHANG Cun1△
1Handan Central Hospital,Handan 056001,Hebei China.
关键词:
维生素D;  椎间盘退变;  细胞凋亡;  线粒体动力学;  AMPK/PGC-1α信号通路
Keywords:
Vitamin D;  intervertebral disc degeneration;  apoptosis;  mitochondrial dynamics;  AMPK/PGC-1α signaling pathway
分类号:
R681.5
DOI:
10.20085/j.cnki.issn1005-0205.260502
文献标志码:
A
摘要:
目的:探讨维生素D对大鼠椎间盘退变的影响及其作用机制。方法:建立针刺诱导的椎间盘退变模型,随机分为假手术组、模型组、维生素D(0.15 μg/kg)组和维生素D(0.15 μg/kg)+腺苷酸活化蛋白激酶(AMPK)抑制剂(Compound C,20 mg/kg)组,每组10只。造模1周后,灌胃/腹腔注射相应药物,1次/d,持续4周。用椎间盘高度指数(DHI)评估椎间盘退变程度; 苏木精-伊红(HE)和番红O-固绿染色观察尾椎间盘病理变化; TUNEL染色检测髓核组织细胞凋亡水平; 免疫组化染色检测髓核组织Aggrecan、基质金属蛋白酶13(MMP-13)、切割的半胱氨酸蛋白酶3(Cleaved Caspase-3)、Bcl-2、Bax表达; 透射电镜观察髓核组织细胞线粒体结构变化; 生化法检测髓核组织三磷酸腺苷含量及线粒体呼吸链复合物Ⅰ/Ⅱ活性水平; Western Blot法检测髓核组织线粒体融合因子(Mfn)1、Mfn2、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、动力相关蛋白1(Drp1)、AMPK及其磷酸化蛋白表达。结果:与假手术组比较,模型组大鼠椎间盘高度指数降低,差异有统计学意义(P<0.05),椎间盘结构紊乱,髓核萎缩、纤维环断裂、软骨终板基质丢失,呈明显退行性改变; 椎间盘髓核组织MMP-13、细胞凋亡率、Cleaved Caspase-3、Bax、p-Drp1/Drp1水平均升高,差异有统计学意义(P<0.05),Aggrecan、Bcl-2、三磷酸腺苷、呼吸链复合物Ⅰ/Ⅱ、Mfn1、Mfn2、p-AMPK/AMPK、PGC-1α水平均降低,差异有统计学意义(P<0.05),且细胞线粒体结构损伤严重。与模型组比较,维生素D组大鼠椎间盘高度指数升高,差异有统计学意义(P<0.05),椎间盘退变显著减轻,结构趋于正常,仅存轻微紊乱; 椎间盘髓核组织MMP-13、细胞凋亡率、Cleaved Caspase-3、Bax、p-Drp1/Drp1水平均降低,差异有统计学意义(P<0.05),Aggrecan、Bcl-2、三磷酸腺苷、呼吸链复合物Ⅰ/Ⅱ、Mfn1、Mfn2、p-AMPK/AMPK、PGC-1α水平均升高,差异有统计学意义(P<0.05),且细胞线粒体结构损伤减轻。Compound C可抑制维生素D对椎间盘退变大鼠的改善作用,差异有统计学意义(P<0.05)。结论:维生素D可延缓大鼠椎间盘退变,恢复线粒体功能,抑制椎间盘髓核组织细胞凋亡,其机制可能与激活AMPK/PGC-1α信号通路,从而改善髓核细胞线粒体动力学平衡有关。
Abstract:
Objective:To investigate the effects of Vitamin D on intervertebral disc degeneration(IDD)in rats and to elucidate its protective mechanism.Methods:An acupuncture-induced IDD model was established.Rats were randomly divided into four groups(n=10 per group):sham-operated group,model group,Vitamin D(0.15 μg/kg)group,and Vitamin D(0.15 μg/kg)+ AMP-activated protein kinase(AMPK)inhibitor(Compound C,20 mg/kg)group.One week after model establishment,the corresponding drugs were administered via gavage/intraperitoneal injection once daily for 4 consecu- tive weeks.The degree of disc degeneration was assessed using the disc height index(DHI).Pathological changes in the caudal intervertebral discs were observed by Hematoxylin-Eosin(HE)and Safranin O-Fast Green staining.The level of apoptosis in nucleus pulposus(NP)tissue was detected by TUNEL assay.Immunohistochemical staining was performed to measure the expression levels of Aggrecan,matrix metalloproteinase 13(MMP-13),Cleaved Caspase-3,B-cell lymphoma 2(Bcl-2),and Bcl-2-associated X protein(Bax)in NP tissue.Mitochondrial structural changes in NP cells were observed using transmission electron microscopy(TEM).Biochemical assays were used to determine the adenosine triphosphate(ATP)content and the activity levels of mitochondrial respiratory chain complexes Ⅰ and Ⅱ in NP tissue.Western Blot was employed to detect the expression of Mitofusin 1(Mfn1),Mitofusin 2(Mfn2),Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),Dynamin-related protein 1(Drp1),AMPK,and its phosphorylated form(p-AMPK).Results:Compared with the sham-operated group,the model group exhibited a significantly lower DHI(P<0.05),disorganized disc structure,atrophy of the nucleus pulposus,rupture of the annulus fibrosus,and loss of cartilaginous endplate matrix,indicating significant degenerative changes.In the NP tissue,the levels of MMP-13,apoptosis rate,Cleaved Caspase-3,Bax,and the p-Drp1/Drp1 ratio were significantly increased(P<0.05),while the levels of Aggrecan,Bcl-2,ATP,respiratory chain complexes Ⅰ/Ⅱ,Mfn1,Mfn2,p-AMPK/AMPK ratio,and PGC-1α were significantly decreased(P<0.05).Severe mitochondrial structural damage was also observed.Compared with the model group,the Vitamin D group showed a significantly higher DHI(P<0.05),a significant mitigation of disc degeneration was observed,characterized by a structural normalization with exhibited only slight disorganization.Concomitantly,the NP tissue showed a marked decrease in several key degenerative indicators,including the levels of MMP-13,apoptotic rate,Cleaved Caspase-3,Bax,and the p-Drp1/Drp1 ratio(P<0.05),while the levels of Aggrecan,Bcl-2,ATP,respiratory chain complexes Ⅰ/Ⅱ,Mfn1,Mfn2,p-AMPK/AMPK ratio,and PGC-1α were significantly increased(P<0.05).Mitochondrial structural damage was also ameliorated.Compound C was found to inhibit the ameliorative effects of Vitamin D on IDD in rats(P<0.05).Conclusion:Vitamin D can delay IDD in rats,restore mitochondrial function,and inhibit apoptosis in nucleus pulposus tissue.Its mechanism of action may be related to the activation of the AMPK/PGC-1α pathway,thereby improving mitochondrial dynamics in nucleus pulposus cells.

参考文献/References:

[1] CHEN X L,ZHANG A R,ZHAO K C,et al.The role of oxidative stress in intervertebral disc degeneration:mechanisms and therapeutic implications[J].Ageing Research Reviews,2024,98:102323.
[2] XIN J G,WANG Y J,ZHENG Z,et al.Treatment of intervertebral disc degeneration[J].Orthopaedic Surgery,2022,14(7):1271-1280.
[3] ZONG Y,LI H,LIAO P,et al.Mitochondrial dysfunction:mechanisms and advances in therapy[J].Signal Transduction and Targeted Therapy,2024,9:124.
[4] HUBENS W H G,VALLBONA-GARCIA A,DE COO I F M,et al.Blood biomarkers for assessment of mitochondrial dysfunction:an expert review[J].Mitochondrion,2022,62:187-204.
[5] 张艳琼,石春霞,张清奇,等.线粒体动力学与细胞骨架的研究进展[J].华南国防医学杂志,2024,38(9):809-812.
[6] REN L M,LI C W,SUN J T,et al.Propionibacterium acnes evades microbicidal phagocytosis by inhibiting the mitochondrial biogenesis of nucleus pulposus cells[J].The FEBS Journal,2026,293(1):295-317.
[7] 高增杰,贾祎佳,覃裕,等.从新视角探讨维生素D基础与临床最新研究进展[J].中国骨质疏松杂志,2025,31(6):930-936.
[8] 杜鑫,宋超,杜冰,等.高海拔地区腰椎间盘突出人群血清25羟维生素D水平变化及意义[J].河北医药,2024,46(12):1805-1809.
[9] LIU W,JIN S W,HUANG M,et al.Duhuo Jisheng decoction suppresses matrix degradation and apoptosis in human nucleus pulposus cells and ameliorates disc degeneration in a rat model[J].Journal of Ethnopharmacology,2020,250:112494.
[10] 朱在师,黄泽灵,陈俊名,等.枳壳甘草汤对椎间盘退变模型大鼠尾椎间盘髓核组织细胞凋亡及Hippo-YAP/TAZ信号通路的影响[J].中医杂志,2025,66(5):509-517.
[11] 贾二霞,徐娜,李帅,等.维生素D介导MEK/ERK通路对妊娠糖尿病大鼠心肌损伤的影响[J].中国临床药理学杂志,2024,40(7):1014-1018.
[12] 魏超,于江,盛关云,等.棕矢车菊素调节AMPK/NLRP3信号通路对骨关节炎大鼠炎性损伤的影响[J].中国药房,2025,36(4):421-426.
[13] KANG L,ZHANG H Q,JIA C Y,et al.Epigenetic modifications of inflammation in intervertebral disc degeneration[J].Ageing Research Reviews,2023,87:101902.
[14] YANG X,CHEN Y,GUO J D,et al.Polydopamine nanoparticles targeting ferroptosis mitigate intervertebral disc degeneration via reactive oxygen species depletion,iron ions chelation,and GPX4 ubiquitination suppression[J].Advanced Science,2023,10(13):2207216.
[15] LAN T,YAN B,GUO W Z,et al.VDR promotes nucleus pulposus cell mitophagy as a protective mechanism against oxidative stress injury[J].Free Radical Research,2022,56(3/4):316-327.
[16] VAJARINTARANGOON L,LIMTHONGKUL W,SINGHATANADGIGE W,et al.Downregulation and hypermethylation of vitamin D receptor in lumbar disc degeneration[J].International Journal of Molecular Sciences,2025,26(7):3226.
[17] XU H W,FANG X Y,CHEN H,et al.Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats[J].Journal of Orthopaedic Research,2024,42(6):1314-1325.
[18] LI X G,WANG B,WANG X N,et al.Vitamin D deficiency promotes intervertebral disc degeneration via p38/NCoR2-mediated extracellular matrix degradation[J].European Journal of Nutrition,2025,64(4):163.
[19] 郭佳霖,何志伟,杨学军.天然小分子治疗椎间盘退变的作用机制研究进展[J].中国脊柱脊髓杂志,2022,32(10):945-953.
[20] 李季霖,周红海,余进爵,等.髓核细胞凋亡相关信号通路研究进展[J].中国脊柱脊髓杂志,2021,31(2):178-182.
[21] 吴高臣,陈金鹏,孟凡剑,等.XIST对椎间盘退变大鼠髓核细胞增殖及细胞外基质合成的影响及其机制[J].解放军医学杂志,2024,49(7):823-831.
[22] ZHANG C,TONG T,MIAO D C,et al.Vitamin D inhibits TNF-α induced apoptosis of human nucleus pulposus cells through regulation of NF-κB signaling pathway[J].Journal of Orthopaedic Surgery and Research,2021,16(1):411.
[23] ZHANG P,RONG K W,GUO J D,et al.Cynarin alleviates intervertebral disc degeneration via protecting nucleus pulposus cells from ferroptosis[J].Biomedicine & Pharmacotherapy,2023,165:115252.
[24] 彭鑫,王志强,张桐,等.线粒体靶向肽SS-31对炎症诱导髓核细胞衰老和焦亡的作用及机制研究[J].中国脊柱脊髓杂志,2025,35(4):399-407.
[25] MIKHAIL A I,NG S Y,MATTINA S R,et al.AMPK is mitochondrial medicine for neuromuscular disorders[J].Trends in Molecular Medicine,2023,29(7):512-529.
(收稿日期:2025-08-13)

备注/Memo

备注/Memo:
基金项目:河北省卫生健康委员会医学科学研究课题计划项目(20231964)
△通信作者 E-mail:13472406598@163.com
更新日期/Last Update: 2026-05-15