蒙药蓝刺头调控FoxO/Wnt/β-catenin通路抗氧化应激防治绝经后骨质疏松研究  

Study on the prevention and treatment of PMOP by antioxidant stress in FoxO/Wnt/β-catenin pathway regulated by Mongolian medicine Echinops sphaerocephalus L.

作　　者：赵军 董重阳 师建平 刘晋 党赢 常虹[4] 海日 李婧 杨广源 ZHAO Jun;DONG Chong-yang;SHI Jian-ping;LIU Jin;DANG Ying;CHANG Hong;HAI Ri;LI Jing;YANG Guang-yuan(Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine,Hohhot 010020,China;Grade 2016 Doctoral Candidate,Nanjing University of Chinese Medicine,Nanjing 210023,China;College of Traditional Chinese Medicine,Inner Mongolia Medical University,Hohhot 010110,China;department of Traditional Chinese Medicine,Hospital Affiliated to Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古自治区中医医院,呼和浩特010020 [2]南京中医药大学,南京210023 [3]内蒙古医科大学中医学院,呼和浩特010110 [4]内蒙古医科大学附属医院中医科,呼和浩特010050

出　　处：《中华中医药杂志》2021年第1期116-121,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：内蒙古医科大学“科技百万工程”联合项目[No.YKD2017KJBW(LH)064];内蒙古自治区第三批老蒙医药中医药专家学术经验继承项目(No.内卫计蒙中字[2019]126);内蒙古自治区草原英才创新团队“中医治未病”项目(No.CYYCTD2018);国家自然科学基金项目(No.30560165);内蒙古自治区自然科学基金项目(No.2009MS1134);国家中医药管理局中医药传承与创新“百千万人才工程”项目(No.J20184832009);第四批全国中医(临床、基础)优秀人才研修项目(No.J20184832009)。

摘　　要：目的:探讨蒙药蓝刺头抗氧化应激防治骨质疏松症(OP)作用;阐明蒙药蓝刺头调控FoxO/Wnt/β-catenin信号通路介导成骨细胞分化、骨形成机制。方法:77只SD雌性大鼠,随机分7组。制备绝经后骨质疏松症(PMOP)模型,阴道上皮角化实验验证造模成功。造模后90d除模型组、假手术组予0.9%氯化钠溶液灌胃,其余各组予相应药物灌胃。采血离心血清;处死剔除双侧完整股骨并标记,右侧股骨4%多聚甲醛溶液固定,左侧股骨-196℃液氮贮存罐保存。右侧股骨采用骨密度仪测定离体骨骨密度(BMD)(股骨近端BMD)。ELISA法测定大鼠血清氧化应激指标。左侧股骨Western Blot法测骨p-p66(S36)、p66、β-catenin、Wnt2、FoxO3a蛋白。结果:蒙药蓝刺头可有效抑制FoxO转录,增强Wnt信号通路调控能力,促进骨成骨分化,使骨形成大于骨吸收;蒙药蓝刺头干预去卵巢PMOP模型大鼠,骨髓间充质干细胞抑制(BMSCs)向成骨方向分化,有效下调破骨细胞(OC)的形成。结论:蓝刺头能显著改善PMOP大鼠氧化应激状态;可交叉调控FoxO/Wnt/β-catenin通路,抑制氧化应激FoxO转录,上调Wnt表达,促进模鼠骨成骨分化、骨形成。Objective:To confirm the effect of antioxidant stress on osteoporosis(OP),elucidate the mechanism of FoxO/Wnt/β-catenin signaling pathway mediated osteoblast differentiation and bone formation,and clarify the related regulatory mechanism and target effect of antioxidant stress of Mongolian medicine Echinops sphaerocephalus L..Methods:Seventyseven SD female rats were randomly divided into seven groups.PMOP model was prepared.Vaginal epithelial keratinization was performed to verify the success of the model.Drug administration:rats in the model group and sham-operated group were given saline intragastric administration 90 days after the establishment of the model,and the other groups were given corresponding drugs intragastric administration.Sample collection:blood centrifugal serum;execute and remove bilateral intact femur and label,right femur was fixed with 4%polyformaldehyde solution,left femur was preserved in liquid nitrogen storage tank at-196℃.Bone mineral density(BMD)of the right femur was measured by bone densitometer(BMD)in vitro(BMD of proximal femur).Serum oxidative stress was measured by ELLISA.Western Blot was used to detect p-p66(S36),p66,β-catenin,Wnt2 and FoxO3 a proteins in the left femur.Results:Mongolian medicine Echinops sphaerocephalus L.can effectively inhibit FoxO transcription,enhance Wnt signaling pathway regulation ability,promote osteogenic differentiation,so that bone formation is greater than bone resorption;Mongolian medicine Echinops sphaerocephalus L.can interfere with ovariectomized PMOP model rats,inhibit BMSCs osteogenic differentiation,effectively down-regulate OC formation.Conclusion:This study shows that the Mongolian medicine Echinops sphaerocephalus L.can significantly improve the oxidative stress state of PMOP model rats,cross-regulate the FoxO/Wnt/β-catenin pathway,inhibit the transcription of oxidative stress FoxO,up-regulate the expression of Wnt,and promote osteogenic differentiation and bone formation in model rats.It can reduce the high conversion index of bone

关 键 词：绝经后骨质疏松症 蒙药 蓝刺头 补暖补精-清镇赫依-固骨质壮骨 氧化应激 FoxO/Wnt-β-catenin通路 分子机制 

分 类 号：R29[医药卫生—民族医学]