p53半剂量缺失纠正1,25(OH)_(2)D_(3)缺乏小鼠的骨质疏松  

p53 heterozygote attenuates osteoporosis phenotype of 1,25(OH)_(2)D_(3) deficient mice

作　　者：张维 倪进荣 周俊[3] 刘畇 张群虎 ZHANG Wei;NI Jinrong;ZHOU Jun;LIU Yun;ZHANG Qunhu(Department of Human Anatomy,Kangda College,Nanjing Medical University,Lianyungang 222000;Department of Orhopedics,the Affiliated Suqian First People’s Hospital of Nanjing Medical University,Suqian 223800;Department of rheumatology and immunology,the Affiliated Suqian First People’s Hospital of Nanjing Medical University,Suqian 223800,China)

机构地区：[1]南京医科大学康达学院基础医学部人体解剖学系,江苏连云港222000 [2]南京医科大学附属宿迁第一人民医院骨科,江苏宿迁223800 [3]南京医科大学附属宿迁第一人民医院风湿免疫科,江苏宿迁223800

出　　处：《南京医科大学学报（自然科学版）》2024年第4期455-461,545,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省高等学校基础科学(自然科学)研究面上项目(22KJB320016);南京医科大学康达学院科研人才培养计划(KD2021KYRC025);宿迁市科技计划资助(KY202214);宿迁市科技计划自然科学基金项目(K202001)。

摘　　要：目的:探索p53半剂量缺失杂合子小鼠能否通过增强抗氧化能力纠正活性维生素D(1,25(OH)_(2)D_(3))缺乏引起的骨质疏松。方法:取10周龄高钙高磷饮食喂养的同窝野生型(wild type,WT)小鼠、p53半剂量缺失杂合子(p53^(+/-))小鼠、1α-羟化酶基因敲除[1α(OH)ase^(-/-)]小鼠及p53半剂量缺失的1α羟化酶基因敲除[1α(OH)ase^(-/-)p53^(+/-)]小鼠的长骨,利用X线、micro-CT、组织病理学和分子生物学等方法,比较各组小鼠血清学、长骨骨矿化、骨形成、骨吸收以及氧化应激等表达变化。结果:与WT小鼠相比,p53^(+/-)小鼠血清钙、磷、甲状旁腺素(parathyroid hormone,PTH)和1,25(OH)_(2)D_(3)水平差异无统计学意义,骨密度、总胶原(total collagen,T-col)阳性面积、成骨细胞数量、碱性磷酸酶(alkaline phosphatase,ALP)和Ⅰ型胶原(collagen type Ⅰ,Col-Ⅰ)阳性面积均有所增加,活性氧水平降低,抗氧化酶SOD1表达增加。与1α(OH)ase^(-/-)小鼠相比,1α(OH)ase^(-/-)p53^(+/-)小鼠血清钙、磷和PTH差异无统计学意义,血清中检测不到1,25(OH)_(2)D_(3),骨密度、T-col阳性面积、成骨细胞数量、ALP和Col-Ⅰ阳性面积均明显增加,破骨细胞数量减少,活性氧水平降低,抗氧化酶SOD1表达增加。结论:p53半剂量缺失可通过增强抗氧化能力纠正1,25(OH)_(2)D_(3)缺乏小鼠的骨质疏松。Objective:To explore whether p53 heterozygote attenuates osteoporosis phenotype of 1,25(OH)_(2)D_(3) deficient mice by enhancing the antioxidant capacity.Methods:The long bones of 10-week-old wild type(WT)mice,p53 heterozygote(p53^(+/-))mice,1α-hydroxylase knockout[1α(OH)ase^(-/-)]mice,and 1α(OH)ase^(-/-)p53^(+/-)mice,fed on a high-calcium and high-phosphorus diet,were analyzed and compared using X-ray,micro-CT,histopathological and molecular biology methods to observe and compare changes in serum levels,bone mineralization,bone formation,bone absorption,and oxidative stress expression.Results:Compared with WT mice,p53^(+/-)mice showed no significant differences in serum calcium,phosphorus,parathyroid hormone(PTH),and 1,25(OH)_(2)D_(3) levels,but had the increased bone density,total collagen(T-col)positive area,osteoblast number,alkaline phosphatase(ALP),and type Ⅰ collagen(col-Ⅰ)positive area,along with the decreased levels of reactive oxygen species and the increased expression of the antioxidant enzyme SOD1.Compared with 1α(OH)ase^(-/-)mice,1α(OH)ase^(-/-)p53^(+/-)mice showed no significant differences in serum calcium,phosphorus,and PTH levels,with undetectable levels of 1,25(OH)_(2)D_(3) in the serum,but showed significantly increased bone density,T-col positive area,osteoblast number,ALP and Col-Ⅰ positive area,decreased osteoclast number and reactive oxygen species levels,and increased expression of SOD1.Conclusion:Half-dose deletion of p53 can attenuate osteoporosis phenotype of 1,25(OH)_(2)D_(3) deficient enhancing the antioxidant capacity.

关 键 词：骨质疏松 P53 1 25(OH)_(2)D_(3) 氧化应激 

分 类 号：R591.44[医药卫生—内科学]