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  

Study on the mechanism of luteolin regulating PI3K/AKT pathway to improve bone loss in a rat model of postmenopausal osteoporosis

作　　者：许勇[1,2] 谢贤斐[1] 颜威 薛彬[1] 熊炎昊[1] XU Yong;XIE Xian-fei;YAN Wei;XUE Bin;XIONG Yan-hao(Department of Orthopedics,Shanghai Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200025;Shanghai Institute of Orthopaedic Injuries,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院伤科,上海200025 [2]上海市伤骨科研究所,上海200025

出　　处：《热带医学杂志》2022年第5期639-643,688,744,共7页Journal of Tropical Medicine

基　　金：上海市科研计划项目(15401901500)

摘　　要：目的探讨木犀草素(Lut)调控磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)通路对绝经后骨质疏松症(PMOP)大鼠模型骨丢失的影响及其作用机制。方法将60只SD大鼠随机分为Sham组、Model组、Lut组(100 mg/kg)、LY294002组(0.3 mg/kg PI3K/AKT通路抑制剂LY294002)、Lut+LY294002组,每组12只。除Sham组外,其它组均进行卵巢切除术构建PMOP大鼠模型,造模成功后,进行药物处理,Sham组、Model组则给予等量的生理盐水处理,每天1次,持续3周。HE染色检测股骨病理变化;双能X射线吸收法检测大鼠股骨骨密度;检测大鼠股骨骨矿盐含量;抗酒石酸磷酸酶(TRAP)染色检测大鼠股骨组织破骨细胞;ELISA法检测大鼠血清中骨保护素(OPG)、细胞核因子κB受体活化因子配基(RANKL)水平;Western blot检测PI3K/AKT通路相关蛋白表达。结果与Sham组比较,Model组骨小梁数目减少,骨小梁间隔变大,骨髓腔变宽,骨密度、骨矿盐含量、OPG水平及p-PI3K/PI3K、p-AKT/AKT表达显著降低,破骨细胞数量、RANKL水平显著升高,差异有统计学意义(P<0.05)。与Model组比较,Lut组骨小梁数目增加,骨小梁间隔变小,骨髓腔变窄,骨密度、骨矿盐含量、OPG水平及p-PI3K/PI3K、p-AKT/AKT表达显著升高,破骨细胞数量、RANKL水平显著降低,差异有统计学意义(P<0.05),而LY294002组对应指标呈现出相反的趋势;与Lut组比较,Lut+LY294002组骨小梁数目减少,骨小梁间隙变大,骨髓腔变宽,骨密度、骨矿盐含量、OPG水平及p-PI3K/PI3K、p-AKT/AKT表达显著降低,破骨细胞数量、RANKL水平显著升高,差异有统计学意义(P<0.05)。结论Lut可能通过激活PI3K/AKT通路改善PMOP大鼠的骨丢失。Objective To investigate the effect of luteolin(Lut)regulating phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway on bone loss in a rat model of postmenopausal osteoporosis(PMOP)and to explore its mechanism of action.MethodsSixty SD rats were randomly divided into Sham group,Model group,Lut group(100 mg/kg),LY294002 group(0.3 mg/kg PI3K/AKT pathway inhibitor LY294002),Lut+LY294002 group,with 12 per group.Except for the Sham group,all other groups underwent ovariectomy to construct a PMOP rat model.After the model was successfully established,they were treated with drugs;the Sham and Model groups were treated with the same amount of normal saline,once a day,for 3 weeks.HE staining was used to detect the pathological changes of the femur;dual-energy X-ray absorption method was used to detect the bone mineral density of rat femurs;the mineral salt content of rat femur bone was detected;anti-tartrate phosphatase(TRAP)staining was used to detect osteoclasts in rat femur tissue;ELISA method was used to detect the levels of osteoprotegerin(OPG)and nuclear factorκB receptor activator ligand(RANKL)in serum;Western blot was used to detect the expression of PI3K/AKT pathway related proteins.ResultsCompared with the Sham group,the number of trabecular bones in the Model group was reduced,the trabecular bone interval became larger,and the bone marrow cavity became wider,the bone mineral density,the content of bone mineral salt,the level of OPG,and the expression of p-PI3K/PI3K and p-AKT/AKT were significantly reduced,and the number of osteoclasts and the level of RANKL were significantly increased,the difference was statistically significant(P<0.05).Compared with the Model group,the number of trabecular bones in the Lut group was increased,the trabecular bone interval became smaller,and the bone marrow cavity became narrower,the bone mineral density,the content of bone mineral salt,the level of OPG,and the expression of p-PI3K/PI3K and p-AKT/AKT were significantly increased,and the number of osteoclasts and the

关 键 词：木犀草素 磷脂酰肌醇3激酶/蛋白激酶B 绝经后骨质疏松症 

分 类 号：R580[医药卫生—内分泌]