糖尿病大鼠一氧化氮与骨代谢变化的研究

Study on changes of serum nitric oxide and bone metabolism in streptozotocin-induced diabetic rats

目的 研究糖尿病 (DM )大鼠血清一氧化氮 (NO)与早期骨代谢改变的关系。方法2 0只SD大鼠分为 2组 ,一组以链脲佐菌素诱导建立糖尿病 (STZ DM )大鼠模型 ,另一为正常对照组 ,测定 2组大鼠的空腹血糖 (FBG)、HbA1c、血清胰岛素、全身、股骨和腰椎骨密度 (BMD)、骨代谢相关指标〔血清钙、骨钙素、降钙素、甲状旁腺素 (PTH)、维生素D3 及尿吡啶酚 /肌酐比〕和血清NO水平。结果 STZ DM大鼠与正常对照组相比 ,血清NO水平显著升高〔(5 1.3± 11.9vs 38.1± 12 .0 )μmol/L ,P <0 .0 1〕 ;全身、股骨和腰椎的BMD显著降低〔(0 .15± 0 .0 7vs 0 .2 1± 0 .0 2 ) g/cm2 ,P<0 .0 1;(0 .16± 0 .0 2vs 0 .19± 0 .0 3) g/cm2 ,P <0 .0 5 ;(0 .12± 0 .0 4vs 0 .18± 0 .0 6 ) g/cm2 ,P <0 .0 5〕 ;血清钙浓度显著升高〔(135 .9± 11.3vs 117.2± 6 .5 )mg/L ,P <0 .0 0 1〕 ,骨钙素水平显著升高〔(0 .0 7± 0 .0 4vs 0 .0 5± 0 .0 1) μg/L ,P <0 .0 5〕 ,维生素D3 水平显著降低〔(7.6± 1.9vs 11.6± 4 .1)μg/L ,P <0 .0 5〕 ,尿吡啶酚 /肌酐显著降低〔(4.8± 0 .8vs 75 .8± 6 0 .7)nmol/mmolCr,P <0 .0 1〕 ;而降钙素和PTH水平改变无统计学意义。相关性分析显示 ,血清NO与尿吡啶酚排泄呈负相关 (r= - 0 .74 ,

Objective To investigate the relationship between serum nitric oxide (NO) and bone metabolism in streptozotocin induced early diabetic (STZ DM) rats. Methods Twenty SD rats were divided into 2 groups, 12 STZ DM rats and 8 controls. Fasting blood glucose, HbA 1c , serum insulin, bone mineral density (BMD) (whole body, lumbar and femoral bone), bone metabolic parameters 〔such as serum calcium, vitamin D 3, parathyroid hormone (PTH), calcitonin, osteocalcin, and urinary pyridinoline/creatinine〕, as well as serum NO were measured. Results Compared with the controls, serum NO in STZ DM group significantly elevated 〔(51.3±11.9 vs 38.1±12.0)μmol/L, P<0.01〕. The BMD in whole body, lumbar and femoral bone significantlydecreased〔(0.15±0.07 vs 0.21±0.02)g/cm 2,P<0.01;(0.16±0.02 vs 0.19±0.03)g/cm 2, P<0.05; (0.12±0.04 vs 0.18±0.06)g/cm 2, P<0.05, respectively〕; Serum calcium and osteocalcin significantly elevated 〔(135.9±11.3 vs 117.2±6.5)mg/L,P<0.001;(0.07±0.04 vs 0.05±0.01)μg/L, P<0.05,respectively〕, while serum vitamin D 3 〔(7.6±1.9 vs 11.6±4.1)μg/L, P<0.05〕andurinarypyridinoline/creatininesignificantlydecreased 〔(4.8±0.8 vs 75.8±60.7)nmol/mmol, P<0.01〕. In correlation analysis, serum NO negatively correlated with urinary pyridinoline/creatinine (r=-0.74, P<0.01), while positively correlated with PTH and Vitamin D 3 (r=0.65, P<0.01; r=0.33, P<0.05). Conclusion There is osteoporosis in early stage of diabetes mellitus, the bone metabolic changes are mainly increased serum calcium and osteocalcin, decreased vitamin D 3 and urinary pyridinoline/creatinine. It suggests that the elevated NO level in diabetes may lead to diabetic osteoporosis through accelerating bone resorption and bone dissolution.