胰岛素抵抗大鼠FGF-23、骨代谢指标、骨超微结构变化及相关性研究  

Serum FGF-23 levels in insulin resistance rats and its relationship with bone metabolism

作　　者：戴静华 赵儒义 常晓岑 郑德禄[5] 温晶 刘媛媛 赵玉岩[1] DAI Jinghua;ZHAO Ruyi;CHANG Xiaoceng(Department of Endocrinology,the First Affiliated Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院内分泌代谢科,沈阳110001 [2]上海市松江区中心医院 [3]上海交通大学附属第一人民医院肿瘤中心 [4]中国医科大学附属第四医院内分泌代谢科 [5]大连大学附属中山医院骨质疏松科 [6]大连医科大学附属第一医院内分泌科

出　　处：《浙江医学》2020年第4期325-329,333,共6页Zhejiang Medical Journal

基　　金：国家自然科学基金面上项目(81470998)。

摘　　要：目的观察胰岛素抵抗(IR)大鼠血清成纤维母细胞生长因子-23(FGF-23)、骨代谢指标和骨超微结构的变化并探讨其相关性。方法将26只雄性SD大鼠随机分为普通饮食(NC)组13只和高脂饮食(HF)组13只,建立IR大鼠模型,高血浆胰岛素-正常血糖钳夹实验进行模型鉴定。测定大鼠血清FGF-23、血糖、胰岛素、脂代谢及骨代谢指标。扫描电镜观察骨组织超微结构。结果HF组大鼠GIR60-120较NC组明显降低(P<0.05),提示IR大鼠模型成功建立。HF组大鼠血清FGF-23、降钙素(CT)较NC组均降低(均P<0.05),血清钙、磷、镁离子较NC组均无统计学差异(均P>0.05),碱性磷酸酶(ALP)、甲状旁腺激素(iPTH)、骨钙素(OC)较NC组均明显增高(均P<0.05)。HF组大鼠血清FGF-23水平与体重、胰岛素及胰岛素抵抗指数(HOMA-IR)均呈负相关(r=-0.844、-0.895、-0.942,均P<0.05),与血清钙、磷、镁、CT、OC、ALP及iPTH无相关性。电镜扫描结果示HF组较NC组骨小梁数目减少,骨小梁间隙增宽,部分区域骨小梁出现裂痕。结论高脂饮食诱导的IR大鼠血清FGF-23水平降低,并存在骨代谢异常及骨超微结构改变,有骨质疏松倾向。FGF-23参与葡萄糖代谢过程,导致IR的发生,同时参与骨质疏松的形成和发展。FGF-23是否可作为2型糖尿病合并骨质疏松的一个早期监测指标,有待进一步研究。Objective To investigate the serum FGF-23 level in insulin resistance(IR)rats and its relationship with bone metabolism.Methods Twenty six male Sprague-Dawley rats were randomly divided into normal diet(NC)group and high-fat diet(HF)group with 13 in each group.IR was induced by high-fat diet and evaluated by hyperinsulinemic euglycemic clamp technique.The levels of serum FGF-23,glucose,insulin,blood lipid and bone metabolism markers were measured.Bone ultrastructure was observed by scanning electron microscopy.Results GIR60-120 in HF group was significantly reduced than that in NC group(P<0.05),IR rat model was successfully established.Levels of serum FGF-23 and calcitonin(CT)were lower in HF group than those in NC group(P<0.05).There was no significant difference in the levels of serum calcium,phosphorus,magnesium between two groups;while levels of ALP,iPTH,OC in HF group were significantly higher than those in NC group(P<0.05).Serum FGF-23 was negatively correlated with weight,insulin and HOMA-IR(r=-0.844,-0.895,-0.942,P<0.05);but not correlated with serum calcium,phosphorus,magnesium,CT,OC,ALP and iPTH in HF group.Electron microscopy showed that the number of bone trabeculae in HF group was decreased,the space between bone trabeculae was widened,and cracks appeared in some areas of bone trabeculae.Conclusion Serum FGF-23 level is decreased in IR rats induced by high-fat diet;bone metabolism markers and bone ultrastructure are changed and there is a tendency of osteoporosis.FGF-23 may be involved in glucose metabolism,leading to insulin resistance,and is also involved in the development of osteoporosis in IR rats,which indicates that FGF-23 may be used as an early monitoring indicator for osteoporosis in patients with type 2 diabetes mellitus.

关 键 词：胰岛素抵抗 成纤维母细胞生长因子-23 骨代谢 骨超微结构 

分 类 号：R580[医药卫生—内分泌] R-332[医药卫生—内科学] R587.2[医药卫生—临床医学]