外源性Shh因子补充对骨质疏松症模型小鼠骨吸收和骨形成能力的影响  

Effects of exogenous Shh factor supplementation on bone resorption and bone formation ability in mouse models of osteoporosis

作　　者：黄华 崔静 曾进海 王荣 彭瀚元 张涛[4] 王璐[1] 曹跃朋 HUANG Hua;CUI Jing;ZENG Jin-hai;WANG Rong;PENG Han-yuan;ZHANG Tao;WANG Lu;CAO Yue-peng(Ward 3,Department of Orthopedics,Beijing Jishuitan Hospital Guizhou Hospital,Guiyang 550014,China;Orthopaedic Ward 11,Beijing Jishuitan Hospital Guizhou Hospital,Guiyang 550014,China;Orthopaedic Ward 10,Beijing Jishuitan Hospital Guizhou Hospital,Guiyang 550014,China;Orthopaedic Ward 9,Beijing Jishuitan Hospital Guizhou Hospital,Guiyang 550014,China;Rheumatology and Immunology Department,The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang,Guiyang 550003,China)

机构地区：[1]北京积水潭医院贵州医院骨内科三病区,贵阳550014 [2]北京积水潭医院贵州医院骨科十一病区,贵阳550014 [3]北京积水潭医院贵州医院骨科十病区,贵阳550014 [4]北京积水潭医院贵州医院骨科九病区,贵阳550014 [5]贵州中医药大学第二附属医院风湿免疫科,贵阳550003

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2024年第4期344-351,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：贵州省卫生健康委员会科学技术项目(gzwkj20210046)。

摘　　要：目的探讨外源性音猬(Sonic Hedgehog,Shh)因子补充对骨质疏松症模型小鼠骨吸收和骨形成能力的影响。方法取健康雌性小鼠48只,随机分为空白对照组、模型组、Shh组,建模和干预后最终分别入组16、8、7只。模型组、Shh组小鼠采取手术切除双侧卵巢构建骨质疏松症模型,Shh组小鼠尾静脉注射2μL Shh液,空白组及模型组尾静脉注射等体积生理盐水,三组均持续干预7 d。观察小鼠组织病理学,比较骨密度值、Shh基因水平、雌二醇(estradiol,E2)、碱性磷酸酶(alkaline phosphatase,ALP)、骨吸收指标[Ⅰ型胶原交联C-末端肽(C-telopeptide of typeⅠcollagen,CTX-Ⅰ)、抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase 5b,TPACP5b)、骨钙素N端中分子片段(N-terminal mid-fragment of osteocalcin,N-MID)水平]、骨形成能力[骨保护素(osteoprotegerin,OPG)、骨钙素(bone gla protein,BGP)、骨特异性碱性磷酸酶(bone specific alkaline phosphatase,BALP)]及破骨细胞分化因子[核因子κB受体活化因子配体(receptor activator of nuclear factor-kappaB ligand,RANKL)]、自噬相关蛋白1(autophagy related protein 1,Beclin-1)、微管相关蛋白1轻链3-Ⅱ(microtubule associated-protein 1 light chain 3-Ⅱ,LC3-Ⅱ)蛋白相对表达量。结果模型组见大量脂肪细胞增生,部分胞核消失或破碎或空骨陷窝;空白对照组髓腔脂肪细胞结构完整、大小及形态均匀;Shh组脂肪细胞形态基本正常、结构完整。空白对照组、Shh组、模型组Shh因子、骨密度值、E2、N-MID、BV/TV、Tb.Th、Tb.N依次明显降低,ALP、CTX-Ⅰ、TPACP5b、Tb.Sp依次明显增高,组间两两比较差异有统计学意义(P<0.05)。模型组OPG、BGP、BALP较空白对照组、Shh组明显低,Shh组也明显低于空白对照组,差异均有统计学意义(P<0.05)。模型组RANKL、Beclin-1、LC3-Ⅱ蛋白相对表达量较空白对照组、Shh组明显高,Shh组也明显高于空白对照组,差异均有统计学意义(P<0.05)。�Objective To investigate the effects of exogenous Sonic Hedgehog(Shh)factor supplementation on bone resorption and bone formation ability in mouse models of osteoporosis.Methods Forty-eight healthy female mice were selected and randomly divided into the blank control group,the model group and Shh group.After modeling and intervention,16,8,and 7 mice were included in the three groups,respectively.Mice in the model group and Shh group were given surgical resection of bilateral ovaries to construct osteoporosis models.Mice in Shh group were injected with 2μL Shh solution through caudal vein.Mice in the blank group and the model group were injected with equal volume of normal saline through caudal vein.All groups were given 7 d of continuous intervention.Histopathology of the three groups was observed.Bone mineral density,Shh level,estradiol(E2),alkaline phosphatase(ALP),bone resorption indicators[C-telopeptide of typeⅠcollagen(CTX-Ⅰ),tartrate-resistant acid phosphatase 5b(TPACP5b)and N-terminal mid-fragment of osteocalcin(N-MID)],bone formation ability[osteoprotegerin(OPG),bone gla protein(BGP)and bone-specific alkaline phosphatase(BALP)]and relative expression levels of receptor activator of nuclear factor-kappaB ligand(RANKL),an osteoclast differentiation factor,Beclin-1,an autophagy-associated protein,and microtubule associated-protein 1 light chain 3-Ⅱ(LC3-Ⅱ)were compared.Results A large number of adipocytes proliferated in the model group,with some disappeared or fragmented nuclei or empty bone lacuna.In the blank control group,the structure of adipocytes in medullary cavity was intact,with uniform size and morphology.The morphology of adipocytes in Shh group was basically normal and the structure was intact.Shh factor level,bone mineral density,E2,N-MID,BV/TV,Tb.Th and Tb.N decreased in sequence,while ALP,CTX-Ⅰ,TPACP5b and Tb.Sp increased in sequence from the blank control group,Shh group to the model group.There were significant differences between any two of the three groups(P<0.05).The levels of

关 键 词：Shh因子 骨质疏松症 小鼠 骨吸收 骨形成 

分 类 号：R681[医药卫生—骨科学]