胰岛素对链脲佐菌素诱导的糖尿病大鼠骨转换和骨力学性能的影响

Effects of insulin on diabetic bone histomorphometric and biomechanical abilities in streptozotocin-treated rats

目的探讨胰岛素对于链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠骨量、骨转换状态和骨力学性能的影响。方法单次尾静脉注射STZ制造糖尿病大鼠模型,成模后分为糖尿病大鼠组(DM)、胰岛素治疗组(INS)与正常对照组(CON),8周后处死,测定3组大鼠血清骨钙素和尿Ⅰ型胶原氨基末端交联肽(NTx)/肌酐(Cr)比值,DEXA方法测定大鼠离体腰椎和股骨骨密度。骨形态计量学方法分析大鼠骨量和骨转换变化情况。采用股骨三点弯曲试验和腰椎压缩试验分析各组大鼠骨力学性能。结果与CON组相比,DM大鼠血清骨钙素和尿NTx/Cr比值降低,DM大鼠腰椎和股骨骨密度降低。与DM组大鼠相比,INS组大鼠血清骨钙素水平增高,尿NTx/Cr比值无变化,INS组大鼠腰椎和股骨骨密度显著增大(P<0.01),但未达CON组水平。骨形态计量学分析提示与CON组相比,DM大鼠骨小梁骨量[TBV/TTV(12.06±2.48)%vs(24.12±1.84)%,P<0.01]减少,骨形成速率减低[(0.44±0.11)vs(0.78±0.14)μm/d,P<0.01]。与DM组大鼠相比,INS组大鼠骨小梁骨量显著增加[TBV/TTV(19.75±2.43)%,P<0.01],骨形成速率亦增加[(0.70±0.16)μm/d,P<0.01]。股骨三点弯曲试验显示,与CON组大鼠相比,DM组大鼠最大载荷、弹性载荷、弯曲能量、最大应力均显著减低(P<0.01)。与DM组相比,INS组上述各力学指标均显著增加(P<0.01),但均未达CON组水平。椎体压缩实验提示与CON组大鼠相比,DM组大鼠最大载荷、弹性载荷、能量吸收、弹性模量均显著减低(P<0.01)。与DM组相比,INS组上述各指标亦显著增加,差异有统计学意义(P<0.01)。结论 DM大鼠表现为低转换型骨量减少,且骨力学性能下降,胰岛素治疗可以促进骨形成,增加骨量,且能改善DM大鼠的骨力学性能。

Objective To study the effect of insulin on bone mass and the condition of bone turnover and bone biomechanical properties in STZ-induced diabetic rats .Methods Of 45 male SD rats studied , 30 were made diabetic by intravenous injection of streptozocin（50 mg/kg） on day-7.Thirty diabetic rats were randomly divided into 2 groups as group DM and control group .DM group were injected subcutaneously with insulin （6 U/kg/d） regularly.After their sacrifice on the day 56, blood was sampled and serum was separated for the measurement of Ca , P, ALPand OC.The left tibia was dissected for bone histomorphometry analysis .Right femur and lumbar vertebrae（L1-L4） were reserved for BMD test.The left femor was separated for three-point bending test,while the fifth lumbar vertibra was prepared for compression test to reflect the biomechanical properties of bone .Results A low-turnover osteopenia was evi-denced in diabetic rats by decreased BMD in both femur and lumbar vertebrae , reduced serum OC level , decreased urine NTx/Cr rati-o, decreased trabecular volume [TBV/TTV（12.06 ±2.48） vs （24.12 ±1.84）%, P〈0.01]and bone formation rate[（0.44 ±0.11） vs （0.78 ±0.14）μm/d, P〈0.01] by bone dynamic study .All these abnormalities except urine NTx/Cr ratio were partly or com-pletely normalized by insulin treatment.The bone densities in vertebrae and femur of diabetic rats significantly decreased （P〈0.01）. Maximal load, elastic load, bending energy , maximal stress in three-point bending test were conducted ,compared with normal control rats.These abnormalities could be partially corrected by insulin teatment （P〈0.01）.In addition,the fifth lumbar vertibrae of diabetic rats were obviously decreased（P〈0.01）, and maximal load,elastic load, energy absorbability and elastic modulus during compressing test.By insulin treatment, these indices partially reversed to the nor-mal control level（P〈0.01）.Conclusion A low-turnover osteope-nia is evidenced in STZ-induced diabetic rats with impaired bone bio-mechanical abilities .All these abnormalities of bone can be partially corrected by the injection of insulin .It shows that insulin can stim-ulate bone formation dramatically while not influence osteoclastic activity in diabetic rats .