天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (3): 171-176.doi: 10.11958/20193706

• 实验研究 • 上一篇    下一篇

机械加载改善高脂饮食诱导的肥胖相关骨丢失

王珂雨，李心乐，刘大全，张平   

  1. 1天津医科大学基础医学院人体解剖与组织胚胎学系（邮编 300070）；2卫生部激素与发育重点实验室，天津市代谢性疾病重点 实验室；3天津市脊柱脊髓重点实验室
  • 收稿日期:2019-12-09 修回日期:2020-01-16 出版日期:2020-03-15 发布日期:2020-04-11
  • 通讯作者: 张平 E-mail:pizhang2008@163.com

Mechanical loading improves bone loss induced by high-fat diet in obese mice

WANG Ke-yu,LI Xin-le,LIU Da-quan,ZHANG Ping   

  1. 1 Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070,China; 2 Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases; 3 Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University
  • Received:2019-12-09 Revised:2020-01-16 Published:2020-03-15 Online:2020-04-11

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摘要： 目的 探究脉冲式关节机械加载对高脂饮食诱导的肥胖小鼠骨丢失的改善作用。方法 将 45只雌性C57BL/6小鼠随机分为普通饮食对照组（Sham组）、高脂饮食模型组（HF组）和高脂加载治疗组（HF+L组），每组 15只。HF组和 HF+L组高脂饮食喂养 4周后，HF+L组进行 4周的机械加载治疗（加载条件为 1 N，10 Hz，3 min/d，每周连续加载 5 d）。治疗结束后测量 3组小鼠体质量指数（BMI）、全身体脂含量和双侧股骨的骨密度。使用 HE染色和MacNeal’s染色分析观察股骨的组织病理改变，使用 Western blot检测成骨生成相关蛋白［碱性磷酸酶（ALP）、Runt相关转录因子 2（RUNX2）］和脂肪生成相关蛋白［过氧化物酶体增殖物激活受体 γ（PPARγ）、CCAAT/增强子结合蛋白 α（C/EBPα）］的表达。结果 与 Sham组相比，HF组小鼠的体脂含量和 BMI升高，骨密度变化率和骨量变化率显著下降，骨小梁面积明显减少，骨髓脂肪细胞增多。机械加载治疗后，HF+L组的骨密度、骨小梁面积比 HF组明显升高，脂肪细胞的数目和面积比 HF 组显著降低（P＜0.05）。Western blot 分析结果表明，HF+L 组与 HF 组相比，ALP 和RUNX2的表达显著升高，C/EBPα和 PPARγ的表达明显降低（均P＜0.05）。结论 机械加载能够有效缓解由肥胖引起的低骨密度和低骨量，其治疗作用可能通过促进成骨分化和抑制脂肪生成来改善骨丢失。

关键词: 机械加载, 肥胖, 骨丢失, 成骨细胞, 脂肪细胞

Abstract: Objective To investigate the effect of mechanical loading on bone loss in obese mice induced by high fat diet. Methods Forty-five female C57BL/6 mice were randomly sorted into three groups: normal control group fed with a standard chow diet (Sham group), high-fat diet group (HF group) and high-fat diet with loading group (HF+L group). There were fifteen mice in each group. After HF group and HF + L group were fed with high-fat diet for 4 weeks, HF+L group was received knee loading for the following 4 weeks (loading condition was 1 N, 10 Hz, 3 min/d, continuous loading for 5 days per week). After the treatment, the changes of body mass index (BMI), total body fat content and bone mineral density of femurs were measured in three groups. HE staining and MacNeal's staining were used to observe the pathological changes of the femur. Western blot assay was used to detect the expressions of osteogenesis-related proteins alkaline phosphatase (ALP),Runt-related transcription factor 2 (RUNX2)] and adipogenesis-related proteins proteasome proliferator-activated receptor γ (PPARγ), CCAAT / enhancer-binding protein α (C/EBPα). Results Compared with the Sham group, the body fat content and BMI were significantly increased in the HF group, and the changes of bone mineral density and bone mineral content were significantly decreased in the HF group. Trabecular bone area ratio was significantly reduced in the HF group, and the accumulation of bone marrow fat cells was significantly increased in the HF group. After mechanical loading treatment, the bone density and trabecular bone area ratio were significantly higher in the HF + L group than those in the HF group, and the number and area ratio of adipocytes were significantly lower than those in the HF group (P＜0.05). Western blot analysis showed that mechanical loading improved the low expressions of ALP and RUNX2 in HF + L group, which were significantly higher than those of HF group, while the C/EBPα and PPARγ were significantly decreased (P＜0.05). Conclusion Mechanical loading can effectively restore low bone mineral density and low bone mass caused by obesity. Its therapeutic effect improves obesity-induced bone loss by promoting osteoblast differentiation and inhibiting adipogenesis.

Key words: mechanical loading, obesity, bone loss, osteoblasts, adipocytes