过量甲状腺激素T3对β2-AR基因敲除小鼠骨代谢的影响  

Effects of Excess Thyroid Hormone T3 on Bone Metabolism inβ2-AR Knockout Mice

作　　者：袁宁 王晓娟 乔彦 何明海 王凤 吉蓉 Yuan Ning;Wang Xiaojuan;Qiao Yan(Department of Endocrinology,Nanchong Central Hospital,Nanchong,Sichuan 637003,China)

机构地区：[1]南充市中心医院内分泌科,四川南充637003

出　　处：《四川医学》2024年第7期721-725,共5页Sichuan Medical Journal

基　　金：南充市市校科技战略合作课题(编号:19SXHZ0173)。

摘　　要：目的研究过量甲状腺激素T3对β2-AR基因敲除小鼠(β2-AR-/-)骨代谢的影响。方法取18只正常C57BL/6J小鼠,分为野生型组、野生型+10倍T3组(35μg/kg)和野生型+20倍T3组(70μg/kg),每组6只。另取18只β2-AR-/-小鼠,分为纯合子组、纯合子+10倍T3组(35μg/kg)和纯合子+20倍T3组(70μg/kg),每组6只。腹腔注射12周,野生型组与纯合子组腹腔注射等量生理盐水。免疫酶联实验(Elisa)检测血清中三碘甲状腺原氨酸(TT3)、四碘甲状腺原氨酸(TT4)、碱性磷酸酶(ALP)、骨桥蛋白(BGP)、骨吸收标志物(CTX)、酒石酸酸性磷酸酶5b(TRAP-5b)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。显微计算机断层扫描(micro-CT)分析小鼠股骨远端,计算骨小梁模式因子(Tb.Pf)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.sp)、骨厚度(Tb.th)、骨链接密度(Conn.Dn)和骨密度(BMD)。结果与T3处理前相比,野生型和纯合子小鼠血清中TT3、TT4、CTX、TRAP-5b、MDA含量均显著性升高,SOD、BGP和ALP含量显著下降,野生型小鼠组织中Tb.Sp升高,Tb.N、Conn.Dn和BMD降低,纯合子+10倍T3小鼠组织中Tb.Pf升高,Tb.Th、Tb.N、Conn.Dn和BMD降低,纯合子+20倍T3小鼠组织中Tb.Th、Tb.Sp升高,Tb.N和Conn.Dn降低(P<0.05);与野生型+10倍T3组相比,20倍浓度T3野生型小鼠血清中TT3、TT4、CTX、TRAP-5b、MDA含量均显著升高,SOD、BGP和ALP含量显著下降,组织中Tb.Pf升高,Tb.Th降低,(P<0.05);与纯合子+10倍T3组相比,纯合子+20倍T3小鼠组织中Tb.Th升高(P<0.05);与野生型+20倍T3组相比,纯合子+20倍T3组小鼠血清中TT3、TT4、BGP、SOD和ALP含量均显著升高,血清中CTX、TRAP-5b、MDA含量均显著性降低,组织中Tb.Th、Tb.N和BMD升高,Tb.Pf和Tb.Sp降低(P<0.05)。结论β2-AR缺乏可能避免小鼠因过量T3作用产生骨代谢异常,减少体内氧化应激损伤,保护骨组织形态。Objective To investigate the effect of excess thyroid hormone T3 on bone metabolism inβ2-AR knockout(β2-AR-/-)mice.Methods 18 normal C57BL/6J mice were divided into wild type group,wild type+10 times T3 group(35μg/kg)and wild type+20 times T3 group(70μg/kg),with 6 mice in each group.Another 18β2-AR-/-mice were divided into homozygote group,homozygote+10 times T3 group(35μg/kg)and homozygote+20 times T3 group(70μg/kg),with 6 mice in each group.After 12 weeks of intraperitoneal injection,the wild-type group and the homozygous group were injected with the same amount of normal saline.Serum triiodothyronine(TT3),tetraiodothyronine(TT4),alkaline phosphatase(ALP),osteopontin(BGP),bone resorption marker(CTX),tartrate acid phosphatase 5b(TRAP-5b),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by immunoenzyme linked immunosorbent assay(Elisa).The distal femurs of mice were analyzed by micro-computed tomography(micro-CT),and trabecular bone was calculated,including trabecular pattern factor(Tb.Pf),trabecular number(Tb.N),trabecular separation(Tb.sp),bone thickness(Tb.Th),bone connection density(Conn.Dn)and bone mineral density(BMD).Results Sp was increased,Tb.N,Conn.Dn and BMD were decreased in wild and homozygote mice.Th,Tb.Sp increased,Tb.N and Conn.Dn decreased in the tissues of homozygous+20 times T3 mice.Compared with the wild type+10 times T3 group,the levels of TT3,TT4,CTX,TRAP-5b and MDA in the serum of 20 times T3 wild type mice were significantly increased,the levels of SOD,BGP and ALP were significantly decreased,the levels of Tb.Pf in the tissues were increased,and Tb.Th in tissues of homozygote+20 times T3 mice were significantly higher than those of homozygote+10 times T3 group(P<0.05);Th,Tb.N and BMD in tissues of homozygote+20 times T3 group were significantly higher than those of wild type+20 times T3 group,while the levels of TT3,TT4,BGP,SOD and ALP in serum of homozygote+20 times T3 group were significantly higher than those of wild type+20 times T3 group,and the levels of CTX,TRAP

关 键 词：甲状腺激素 Β2-AR 基因敲除 骨代谢 

分 类 号：R-332[医药卫生]