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

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

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。

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-I31）. OBJECTIVE： To study the changes of estrogen, NO, and TGF-βI 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 ELISAmethod, and the content of TGF-βI 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.