糖尿病性骨质疏松模型雌激素、一氧化氮及转化生长因子β1的变化

背景:糖尿病和卵巢去势是骨质疏松发生的两大主要原因,均会出现一氧化氮和转化生长因子β1的变化。目的:探讨雌激素、一氧化氮、转化生长因子β1在糖尿病性骨质疏松模型中的变化及意义。方法:采用链脲佐菌素诱导制备糖尿病大鼠模型,于造模后4,8,12,16周,进行骨密度检测,并应用放免法检测血清雌激素水平,硝酸还原酶法检测血清一氧化氮水平,ELISA法检测血清转化生长因子β1水平,免疫组织化学法检测骨中转化生长因子β1水平。结果与结论:随着链脲佐菌素诱导时间的延长,糖尿病大鼠股骨骨密度逐渐降低(P<0.05或P<0.01);血清一氧化氮水平逐渐降低(P<0.05或P<0.01);血清转化生长因子β1水平逐渐升高(P<0.01);血清雌激素水平轻度降低,与同时间点正常大鼠比较差异无显著性意义(P>0.05)。免疫组织化学结果显示转化生长因子β1主要表达于成骨细胞的胞浆中,其阳性表达随链脲佐菌素诱导时间的延长逐渐下降(P<0.01)。说明糖尿病大鼠血清一氧化氮水平和骨组织中转化生长因子β1水平的变化导致了骨吸收增加,骨形成减少,使骨密度降低,参与了糖尿病性骨质疏松的发生。

Changes of estrogen, nitric oxide and transforming growth factor beta 1 in rats with diabetic osteoporosis

BACKGROUND:Diabetes mellitus and ovariectomy are two main reasons for osteoporosis,both of which can lead to variations in nitric oxide(NO) and transforming growth factor β1(TGF-β1).OBJECTIVE:To study the changes of estrogen,NO,and TGF-β1 in the rats with diabetic osteoporosis.METHODS:Rats with diabetic osteoporosis were induced by streptozotocin(STZ).The bone mineral density(BMD) was measured at 4,8,12 and 16 weeks after model preparation;the serum estrogen levels was measured by radioimmunoassay method,serum NO levels ere detected by nitrate reduction method,serum TGF-β1 levels determined by ELISA method,and the content of TGF-β1 in the bone tissues was measured by the immunohistochemical method.RESULTS AND CONCLUSION:With induction time prolonged,BMD of femur was gradually decreased(P < 0.05 or P < 0.01),serum NO level decreased(P < 0.05 or P < 0.01),serum TGF-β1 level increased(P < 0.01).The estrogen level in the model group was slightly decreased,but the difference had no significance(P > 0.05).Immunohistochemical results showed that TGF-β1 was mainly expressed in the osteoblast cytoplasm,and the number of positive cells was gradually decreased with induction time prolonged(P < 0.01).The changes of serum NO and TGF-β1 in bone tissues result in lower bone mineral density because of increasing bone absorption and decreasing bone formation.Nitric oxide and TGF-β1 play an important role in diabetic osteoporosis.