[1]夏静,唐光平△,李小平,等.木犀草素调控STAT1/Caspase-3通路对激素性股骨头坏死大鼠组织形态的影响[J].中国中医骨伤科杂志,2026,34(03):36-42.[doi:10.20085/j.cnki.issn1005-0205.260306]
　XIA Jing,TANG Guangping,LI Xiaoping,et al.Effect of Luteolin on the Tissue Morphology of Steroid-Induced Osteonecrosis of the Femoral Head in Rats by Regulating STAT1/Caspase-3 Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(03):36-42.[doi:10.20085/j.cnki.issn1005-0205.260306]
点击复制

木犀草素调控STAT1/Caspase-3通路对激素性股骨头坏死大鼠组织形态的影响()

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

卷:
第34卷
期数:
2026年03期
页码:
36-42
栏目:
基础研究
出版日期:
2026-03-15

文章信息/Info

Title:
Effect of Luteolin on the Tissue Morphology of Steroid-Induced Osteonecrosis of the Femoral Head in Rats by Regulating STAT1/Caspase-3 Pathway
文章编号:
1005-0205(2026)03-0036-07
作者:
夏静1; 唐光平1△; 李小平1; 靳艳1
1武汉市中医医院(武汉,430050)
Author(s):
XIA Jing1; TANG Guangping1△; LI Xiaoping1; JIN Yan1
1Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430050,China.
关键词:
木犀草素;  STAT1/Caspase-3通路;  激素性股骨头坏死;  大鼠;  组织形态
Keywords:
luteolin;  STAT1/Caspase-3 pathway;  steroid-induced osteonecrosis of femoral head;  rats;  morphology
分类号:
R285.5
DOI:
10.20085/j.cnki.issn1005-0205.260306
文献标志码:
A
摘要:
目的:探究木犀草素调控信号转导与转录激活因子1-半胱氨酸天冬氨酸特异性蛋白酶3(STAT1/Caspase-3)通路对激素性股骨头坏死大鼠组织形态的影响。方法:将大鼠随机分为对照组、模型组、木犀草素低/高剂量组、高剂量木犀草素+氟达拉滨(STAT1激活剂)组。酶联免疫吸附法(ELISA)检测大鼠血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、骨碱性磷酸酶(BALP)、Ⅰ型前胶原氨基端前肽(PINP)、抗酒石酸酸性磷酸酶(TRAP)和β-胶原降解产物(β-CTX)水平; 检测股骨结构和骨组织细胞凋亡; 苏木精-伊红(HE)染色检测股骨组织形态; 蛋白免疫印迹法检测Runt相关转录因子2(Runx2)、骨形态发生蛋白2(BMP-2)、活化的半胱氨酸天冬氨酸蛋白酶-3(Cleaved Caspase-3)和STAT1/Caspase-3通路蛋白水平。结果:与对照组比较,模型组大鼠股骨头结构明显被破坏,股骨头组织有明显损伤,血清IL-1β、IL-6、TNF-α、TRAP和β-CTX水平,骨小梁分离度(Tb.Sp)、空骨陷窝率、骨组织细胞凋亡率,Cleaved Caspase-3、p-STAT1/STAT1和Caspase-3蛋白表达水平升高,血清BALP和PINP水平,骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)水平,骨组织Runx2和BMP-2蛋白表达水平降低,差异有统计学意义(P<0.05)。与模型组比较,木犀草素低/高剂量组大鼠股骨头结构破坏程度减轻,股骨头组织形态有明显改善,血清IL-1β、IL-6、TNF-α、TRAP和β-CTX水平,Tb.Sp、空骨陷窝率、骨组织细胞凋亡率,Cleaved Caspase-3、p-STAT1/STAT1和Caspase-3蛋白表达水平降低,血清BALP和PINP水平,BV/TV、Tb.N、Tb.Th水平,骨组织Runx2和BMP-2蛋白表达水平升高,差异有统计学意义(P<0.05); 氟达拉滨可降低木犀草素对股骨头坏死大鼠骨组织形态的改善作用,差异有统计学意义(P<0.05)。结论:木犀草素减轻股骨头坏死大鼠股骨头组织损伤可能与抑制STAT1/Caspase-3通路有关。
Abstract:
Objective:To discuss the effect of luteolin on the tissue morphology of steroid-induced osteonecrosis of femoral head(SONFH)rats by regulating signal transducer and activator of transcription 1(STAT1)/Cysteinyl aspartate specific proteinase 3(Caspase-3)pathway.Methods:Rats were randomly grouped into the control group,model group,luteolin low-dose group,luteolin high-dose group,and luteolin high-dose + Fludarabine(STAT1 activator)group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),bone alkaline phosphatase(BALP),procollagen I N-terminal propeptide(PINP),tartrate-resistant acid phosphatase(TRAP),and β-collagen degradation product(β-CTX)in rat serum.The apoptosis of femoral structure and bone tissue cells was detected.Hematoxylin-Eosin(HE)staining was performed to detect the morphology of femoral tissue.Western Blot was performed to detect the Runt-related transcription factor 2(Runx2),bone morphogenetic protein-2(BMP-2),Cleaved cysteine-aspartic acid protease-3(Cleaved Caspase-3),and STAT1/Caspase-3 pathway proteins.Results:For the control group,the femoral head structure of rats in the model group was markedly destroyed,and the femoral head tissue was prominently damaged.The serum IL-1β,IL-6,TNF-α,TRAP and β-CTX,trabecular separation(Tb.Sp),empty bone resorption rate,bone tissue cell apoptosis rate,Cleaved Caspase-3,p-STAT1/STAT1 and Caspase-3 proteins were increased,while the serum BALP and PINP,bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),and the bone tissue Runx2 and BMP-2 proteins were decreased(P<0.05).For the model group,the degree of structural damage to the femoral head of rats in the luteolin low-dose,luteolin high-dose groups was reduced,and the morphology of the femoral head tissue was prominently improved.The serum IL-1β,IL-6,TNF-α,TRAP and β-CTX,Tb.Sp,empty bone resorption rate,bone tissue cell apoptosis rate,Cleaved Caspase-3,p-STAT1/STAT1 and Caspase-3 proteins were decreased,while the serum BALP and PINP,BV/TV,Tb.N,Tb.Th,and the bone tissue Runx2 and BMP-2 proteins were increased(P<0.05).Fludarabine could reduce the improvement effect of luteolin on bone tissue morphology in SONFH rats(P<0.05).Conclusion:Luteolin may alleviate femoral head tissue damage in SONFH rats by inhibiting STAT1/Caspase3 pathway.

参考文献/References:

[1] LIU Q,WU Y Y,LI S S,et al.Ursolic acid alleviates steroid-induced avascular necrosis of the femoral head in mouse by inhibiting apoptosis and rescuing osteogenic differentiation[J].Toxicology and Applied Pharmacology,2023,475:116649.
[2] WU J F,CHEN T,ZHANG M H,et al.Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release[J].Archives of Toxicology,2024,98(10):3365-3380.
[3] SUN Y Q,LIANG M M,XING Y M,et al.Cyasterone has a protective effect on steroid-induced osteonecrosis of the femoral head[J].PLoS One,2023,18(10):e0293530.
[4] ZHU M T,SUN Y P,SU Y,et al.Luteolin:a promising multifunctional natural flavonoid for human diseases[J].Phytotherapy Research,2024,38(7):3417-3443.
[5] YAN Z J,ZHAN J D,QI W H,et al.The protective effect of luteolin in glucocorticoid-induced osteonecrosis of the femoral head[J].Frontiers in Pharmacology,2020,11:1195.
[6] XU X,FAN X Y,WU X J,et al.Luteolin ameliorates necroptosis in Glucocorticoid-induced osteonecrosis of the femoral head via RIPK1/RIPK3/MLKL pathway based on network pharmacology analysis[J].Biochemical and Biophysical Research Communications,2023,661:108-118.
[7] 龚高进,黄海汛.齐墩果酸调节Wnt/β-catenin信号通路减轻大鼠激素性股骨头坏死[J].中国组织工程研究,2024,28(27):4373-4377.
[8] LIN J,QI W H,CHEN K,et al.Downregulating STAT1/caspase-3 signaling with fludarabine to alleviate progression in a rat model of steroid-induced avascular necrosis of the femoral head[J].Journal of Biochemical and Molecular Toxicology,2019,33(4):e22265.
[9] DUAN P,WANG H Y,YI X,et al.C/EBPα regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPARγ signalling pathway[J].Stem Cell Research & Therapy,2022,13(1):342.
[10] ÖZMEN E,IZOL ÖZMEN H,ATASOY S,et al.The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis[J].Acta Orthopaedica et Traumatologica Turcica,2023,57(5):237-242.
[11] CUI Y,HUANG T,ZHANG Z,et al.The potential effect of BMSCs with miR-27a in improving steroid-induced osteonecrosis of the femoral head[J].Scientific Reports,2022,12:21051.
[12] YUAN N,ZHANG W Y,YANG W Z,et al.Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation,promoting bone formation and inhibiting bone resorption[J].Journal of Orthopaedic Surgery and Research,2024,19(1):243.
[13] 张宗逸,吴港归,朱守旭,等.骨痹通消颗粒调控TGF-β1/Smads信号通路干预激素性股骨头坏死大鼠模型[J].安徽中医药大学学报,2025,44(2):88-93.
[14] JUN J Y,KIM J H,KIM M,et al.Persicae semen promotes bone union in rat fractures by stimulating osteoblastogenesis through BMP-2 and Wnt signaling[J].International Journal of Molecular Sciences,2023,24(8):7388.
[15] WANG Y Y,ZHAN Y Q,JI C X,et al.Houttuynia cordata Thunb repairs steroid-induced avascular necrosis of the femoral head through regulating NF-κB signaling pathway[J].Toxicon,2023,233:107270.
[16] 许勇,谢贤斐,颜威,等.木犀草素调控PI3K/AKT通路改善绝经后骨质疏松症大鼠模型骨丢失的机制[J].热带医学杂志,2022,22(5):639-643.
[17] CHAI S,YANG Y B,WEI L W,et al.Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling[J].Phytomedicine,2024,128:155516.
[18] CAI T W,CHEN S Y,WU C H,et al.Erythropoietin suppresses osteoblast apoptosis and ameliorates steroid-induced necrosis of the femoral head in rats by inhibition of STAT1-caspase 3 signaling pathway[J].BMC Musculoskeletal Disorders,2023,24(1):894.
[19] FENG Z H,ZHENG W H,TANG Q,et al.Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats[J].Apoptosis,2017,22(8):1001-1012.
[20] 许心弦,胡月正,柳海晓.促红细胞生成素通过调控STAT1-caspase3信号通路治疗激素性股骨头坏死的实验研究[J].浙江创伤外科,2023,28(9):1601-1604.
(收稿日期:2025-06-19)

备注/Memo

备注/Memo:
基金项目:湖北省中医药管理局中医药科研项目(ZY2023Z011)
△通信作者 E-mail:nlnhvl@163.com
更新日期/Last Update: 2026-03-15