骨细胞GLP-1受体表达对2型糖尿病大鼠骨微结构的影响

目的观察2型糖尿病大鼠股骨颈骨细胞表达胰高血糖素样肽-1受体(GLP-1R)阳性细胞百分数的变化,探讨骨组织GLP-1R变化对骨微结构的影响。方法雄性Wistar大鼠60只,随机分为实验组(30只)和对照组(30只),实验组采用高糖高脂饲料喂养至12周时加小剂量链脲佐菌素腹腔注射诱导糖尿病模型,对照组采用普通饲料喂养。分别于造模成功时和成模后第12周,处死10只大鼠作为糖尿病0周组(DM0w组,n=10)和糖尿病12周组(DM12w组,n=10),对照组分别于同期各处死10只大鼠作为正常对照(NGT0w组,n=10;NGT12w组,n=10)。经腹主动脉采血测定空腹血糖(FBG)、胆固醇(TC)、三酰甘油(TG)。取近端股骨颈,制备脱钙和不脱钙骨切片,备免疫组化检测GLP-1R阳性的骨细胞,采用Simple软件分析骨小梁形态计量学指标:骨小梁占骨髓腔体积百分比(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)。采用单因素方差分析比较各组大鼠股骨颈表达GLP-1R阳性的骨细胞百分数,BV/TV、Tb.Th、Tb.N的变化,采用Pearson行相关分析。结果与同期对照组相比,DM0w组、DM12w组大鼠FBG、TC、TG升高(均P0.05);与同期对照组相比,DM0w组、DM12w组大鼠股骨颈表达GLP-1R阳性骨细胞百分数和BV/TV、Tb.Th均减少(均P0.05);与DM0组相比,DM12组大鼠股骨颈表达GLP-1R阳性的骨细胞百分数、BV/TV、Tb.Th、Tb.N均减少(均P0.05);Pearson相关分析显示大鼠股骨颈GLP-1R阳性骨细胞百分数与股骨颈BV/TV、Tb.Th、Tb.N均呈正相关,相关系数分别为r=0.803,P0.05;r=0.545,P0.05;r=0.771,P0.05。结论糖尿病大鼠股骨颈骨细胞GLP-1R的表达减少,同时BV/TV、Tb.N减少,Tb.Th变薄,骨细胞GLP-1R的表达可能是影响2型糖尿病骨微结构的因素之一。

Affect of GLP-1 receptor expressed of bone cells on the bone microstructure in the type 2 diabetic rats

Objective To observed the changes of glucagon-like peptide-1 receptor （GLP-1R） expressed on the bone cells of femoral neck in type 2 diabetic rats , and to investigate the effects of this changes on the bone microstructure . Methods 60 Male Wistar rats were divided into experimental group （ 30 ） and control group （ 30 ） , the experimental group were fed with high-sugar and high-fat diet, then a small dose of streptozotocin intraperitoneal was injected in 12 weeks, while the control group were fed with normal diet .Each groups were sacrificed , then the proximal femoral neck were cut off when successful modeling as DM0 group （n=10） and DM12 group （n=10） respectively after 12 weeks.Fasting glucose （ FBG） , cholesterol （ TC） and triglyceride （ TG） were assayed in specimens from abdominal aortic .Preparation of slices of bone tissue with decalcification and without , to observe GLP-1R-positive bone cells chemistry .Trabecular morphology were measured with simple software：volume percentage of trabecular account marrow cavity volume （ BV/TV） , trabecular thickness （ Tb.Th ） , trabecular bone number （ Tb.N ） .One-way ANOVA were used to compare the differences between these indicators .Pearson correlation analysis were used to explore the correlation between them .Results （1） Compared with the control group in the same period , DM0w and DM12w groups＆#39;FBG, TC, TG, were increased （ P〈0.05 ） .（ 2 ） Compared with the control group in the same period , the percentage numbers of bone cells which express GLP-1R were reduced in DM0w and DM12w groups （P〈0.05）, BV/TV and Tb.Th were reduced （P〈0.05）.（3） Compared with DM0w group, the percentage numbers of GLP-1R positive bone cell on femoral neck , and BV/TV, Tb.Th, Tb.N of DM12w groups were reduced （P〈0.05）.（4） Pearson correlation analysis between the percentage of GLP-1R positive bone cells and BV/TV, Tb.Th, Tb.N showed a positive correlation, correlation coefficients were （r=0.803, P〈0.05;r=0.545, P〈0.05; r=0.771, P〈0.05）.Conclusion The expression of GLP-1R on the bone cells were decreased, while BV/TV, Tb.N were reduced, and Tb.Th were thinning in diabetic rats.So the expression of GLP-1R on bone cells may be one of the factors which affect bone microstructure in type 2 diabetes.