摘要
目的在高脂饮食(HFD)诱导的肥胖雄鼠中探究雌激素相关受体alpha(ERR)拮抗剂Compound 29对小鼠骨量的改善作用。方法C57BL/6J雄鼠随机分为HFD组、“HFD+Compound 29”组(“HFD+C29”组)和普通饮食组(CD组),每组各6只。在整个实验过程中,HFD组和“HFD+C29”组小鼠用高脂饲料喂养,CD组小鼠用普通饲料喂养。喂养18周后,“HFD+C29”组小鼠每天Compound 29灌胃给药,CD组和HFD组小鼠等量溶剂灌胃,持续3周。最后进行口服葡萄糖耐量试验(OGTT)并处死小鼠收集样品。用微计算机断层扫描技术对右股骨进行骨组织形态学分析,左股骨石蜡包埋切片后分别进行苏木素伊红(HE)和抗酒石酸酸性磷酸酶(TRAP)染色,用酶联免疫吸附测定法检测血浆I型胶原交联羧基末端肽(CTX-I)浓度。结果骨扫描和HE染色结果显示与CD组相比,HFD组小鼠骨密度、骨小梁数量和厚度减少,HFD组小鼠发生骨量丢失;Compound 29给药后,HFD小鼠骨密度和骨量得到明显改善。TRAP染色和CTX-I浓度检测结果表明Compound 29给药后,HFD小鼠破骨细胞数量减少,骨吸收减弱。此外,OGTT结果显示Compound 29提高HFD小鼠糖耐受能力。结论ERR拮抗剂Compound 29改善HFD诱导的肥胖雄鼠的骨丢失。
Objective To investigate the effect of Compound 29, a selective antagonist of Estrogen-related receptor alpha(ERR), on bone mass in mice with obesity induced by high-fat diet(HFD). Methods C57 BL/6 J male mice were randomly divided into HFD group, "HFD+Compound 29" group( "HFD+C29" group) and standard chow diet group(CD group), 6 mice in each group. Throughout the experiment, HFD group and "HFD+C29" group were fed high-fat diet, CD group were fed standard chow diet. After 18 weeks of feeding, "HFD+C29" group was treated with Compound29 daily by oral gavage for 3 weeks, CD group and HFD group were treated with the same amount of solvent by oral gavage. At the end of the experiment, mice were given glucose by gavage for oral glucose tolerance test(OGTT), then mice were sacrificed and samples were collected. The right femur was scanned by Micro-CT for bone histomorphological analysis and the left femur was decalcified, embedded in paraffin and then cut into sections for haematoxylin and eosin(HE) and tartrate-resistant acid phosphatase(TRAP) staining. Plasma C-terminal telopeptide 1 chain of type I collagen(CTX-I) was measured by ELISA. Results Bone scan and HE staining showed that compared with CD group, the bone mineral density, trabecula number and thickness in HFD group mice were reduced, and the bone mass was lost. After Compound 29 treatment, the bone mineral density and bone mass in HFD mice were increased. The results of CTX-I measurement and TRAP staining showed that the osteoclast number and bone resorption in HFD mice were decreased after Compound 29 treatment. In addition, Compound 29 treatment improved glucose tolerance in HFD mice according to OGTT results. Conclusion Compound 29 as a selective antagonist of ERRα protects HFD-induced obese male mice from bone loss.
作者
钟丽红
卢兆成
黄童龄
杨萌
段锐
管敏
Zhong Lihong;Lu Zhaocheng;Huang Tongling;YangMeng;Duan Rui;GuanMin(Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen Guangdong,518055;University of Chinese Academy of Sciences,Beijing,100049;School of Physical Education and Sports Science,South China Normal University,Guangzhou Guangdong,510631,China)
出处
《生物骨科材料与临床研究》
CAS
2021年第3期24-29,共6页
Orthopaedic Biomechanics Materials and Clinical Study
基金
科技部国家重点研发计划(2018YFA0703100)
国家自然科学基金项目(82072493,81770882)
广东省特支计划(2017TQ04R394)
深圳市科技研究资助计划(KQJSCX20180330170052049,20170502171625936)。
