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OA
Effect of Luteolin on the Tissue Morphology of Steroid-Induced Osteonecrosis of the Femoral Head in Rats by Regulating STAT1/Caspase-3 Pathway
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.
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 phos-phatase(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-relat-ed 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).Fludara-bine 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.
夏静;唐光平;李小平;靳艳
武汉市中医医院(武汉,430050)武汉市中医医院(武汉,430050)武汉市中医医院(武汉,430050)武汉市中医医院(武汉,430050)
医药卫生
木犀草素STAT1/Caspase-3通路激素性股骨头坏死大鼠组织形态
luteolinSTAT1/Caspase-3 pathwaysteroid-induced osteonecrosis of femoral headratsmorphology
《中国中医骨伤科杂志》 2026 (3)
36-42,7
湖北省中医药管理局中医药科研项目(ZY2023Z011)
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