骨钙素与2型糖尿病发病关系的实验研究

目的 探讨骨钙素(BGP)对2型糖尿病(T2DM)大鼠β细胞功能及糖脂代谢的影响,为T2DM的防治提出新理念.方法 将24只SD大鼠随机分2组,即NC组和DM组,各12只.第8周末,DM组按25 mg/kg腹腔注射STZ造模,NC组注射相应无菌枸橼酸钠溶液作对照,第10周末行OGTT筛选成模大鼠.第4、8、10、14周末分别取血检测BGP、糖脂及胰岛素代谢相关指标.14周末处死所有大鼠,胰腺组织用HE染色并在光镜下观察病理改变,用免疫组化SP法检测BGP在胰腺组织表达情况.结果 第8、14周末DM组TG、TC、空腹胰岛素(FINS)水平均明显高于同周数NC组(P<0.001),HDL-C、胰岛素敏感性(ISI)水平均低于同周数NC组(P<0.001),但DM组8周末时BGP较NC组轻度升高,14周末时较NC组明显降低.14周末2组BGP在β细胞含量比较,DM组显著减少(P<0.001).Pearson相关分析显示,血清BGP水平与FPG、TG、TC呈负相关(P<0.05),与FINS、ISI、HDL-C、胰腺组织BGP呈正相关(P<0.05).结论 实验T2DM大鼠在糖脂代谢紊乱的同时,伴血清BGP和其在β细胞表达水平减少,提示T2DM发病与BGP有关联.

An experimental study on the relationship between osteocalcin and the pathogenesis of type 2 diabetesmemtus

Objective To investigate the effect of BGP on the function of β-cell, glucose and lipid metabolism in type 2 diabetes mellitus, then propose new ideas to the prevention and treatment of type 2 diabetes mellitus. Methods 24 Sprague-Dawlay rats were randomly divided into two groups, the NC and DM group,twelve in each one. At the end of the 8th week, STZ （25 mg/kg）were injected into abdominal cavity in DM group, Sodium citrate solution were injected in NC group as control. At the end of the 10th week,diabetic rats model were made by oral glucose talerance test（OGTF）. The blood sample was collected separately at the end of the 4th, 8th, 10th and 14th week, the level of BGP, insulin, glucose and lipid metabolism in serum were tested. At the end of 14th week, all the rats were killed, the pancreatic tissue was dyed with HE, then we can observe pathological changes by light microscope, detect the expression of BGP by immunohistochemieal stretavidin proxidase （SP） method. Results At the end of the 8th, 14th week ,TG,TC, FINS in DM group were significantly higher than the NC group （P 〈 0. 001 ）, HDL- C ,ISI were lower than the index in NC group（ P 〈 0. 001 ）at the same time, but at the end of the 8th BGP in DM group were mildly higher than the NC group, at the end of the 14th BGP in DM group were significantly decreased compared with the NC group. At the end of the 14th week,the BGP in 13-cell was apparently reduced in DM group compared with the NC group（ P 〈 0. 001 ）. Pearson linear correlation analysis showed that the levels of BGP in serum were negative with FPG, TG, TC （P 〈 0. 05）, and were inverse correlation with FINS, ISI, HDL-C and the expression of pancreas BGP （P 〈 0.05 ）. Conclusions Except helipid disorders rI＇2DM rats, we found that BGP and its expression level decreased in the β-cells in serum at the same time, suggesting that the incidence of T2DM is associated with BGP.