Ren Hui, Shen Gengyang, Jiang Xiaobing, Liang De, Tang Jingjing, Cui Jianchao, Lin Shunxin, Zhuang Hong, Yang Zhidong, Zhang Shuncong, Yao Zhensong
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015 Mar;29(3):307-14.
To analyze the phasic changes of bone mass, bone turnover markers, and estrogen levels at different time points after glucocorticoid (GC) intervention in rat and their correlation.
Thirty-four female 3-month-old Sprague Dawley rats were randomly divided into the following 3 groups: baseline group (n = 6), dexamethasone (DXM) group (n = 14), and control group (n = 14). Rats were injected with DXM at the dose of 0.75 mg/kg, twice a week for 12 weeks in DXM group, with salt solution lavage in control group, and no treatment was given in baseline group. The body mass, adrenal weight, and uterus weight were measured. Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) of lumbar vertebral and femurs were detected by dual energy X-ray absorptiometry. Meanwhile, the serum levels of N-terminal propeptide of type I procollagen (PINP), C-terminal cross-linking telopeptide of type I collagen (β-CTX), and estrogen levels were determined by ELISA before experiment in baseline group and at 4, 8, and 12 weeks after experiment in control and DXM groups. At last, the correlation was analyzed among body weight, BMD, PINP, β-CTX, estrogen levels, and GC intervention duration of DXM group.
The body mass, adrenal weight, and uterus weight in DXM group were signiflcantly lower than those in baseline group and control group at all the time points (P < 0.05). The levels of PINP and β-CTX elevated slowly in DXM group, significant difference was found at 12 weeks (P < 0.05), but no significant difference at the 4 and 8 weeks (P > 0.05) when compared with those in baseline group and control group. The estrogen level in DXM group was significantly lower than that in baseline group and control group at all the time points (P < 0.05). BMD, BMC, and BA of lumbar vertebral and femurs in DXM group were significantly lower than those in control group at all the time points after GC intervention (P < 0.05). Loss of bone mass of L2 and femoral trochanteric region in DXM group was the lowest of all ranges of interest (ROIs). BMC and BA of lumbar vertebrae and BA of femoral shaft in DXM group at 4 weeks were significantly lower than those in baseline group (P < 0.05). But there was no significant difference in BMD, BMC, and BA of other lumbar vertebrae and femurs' ROIs between DXM group and baseline group at all the time points (P > 0.05). After GC intervention, BMD of lumbar vertebrae and femurs had negative correlation with PINP and β-CTX (P < 0.05) and positive correlation with estrogen level (P < 0.05).
The bone mass decreases rapidly at the early stage after GC intervention and then maintains a low level with time, the levels of bone turnover markers show a progressive increase, and the estrogen levels show a decrease trend. In addition, body weight, the levels of bone turnover markers and estrogen are associated with the change of bone mass.
分析糖皮质激素(GC)干预大鼠后不同时间点骨量、骨转换标志物及雌激素水平的阶段性变化及其相关性。
将34只3月龄雌性Sprague Dawley大鼠随机分为3组:基线组(n = 6)、地塞米松(DXM)组(n = 14)和对照组(n = 14)。DXM组大鼠以0.75 mg/kg的剂量注射DXM,每周2次,共12周;对照组用盐溶液灌洗;基线组不进行处理。测量大鼠体重、肾上腺重量和子宫重量。采用双能X线吸收法检测腰椎和股骨的骨密度(BMD)、骨矿物质含量(BMC)和骨面积(BA)。同时,在基线组实验前以及对照组和DXM组实验后4、8和12周,通过酶联免疫吸附测定法测定血清I型前胶原N端前肽(PINP)、I型胶原C端交联端肽(β-CTX)水平以及雌激素水平。最后,分析DXM组体重、BMD、PINP、β-CTX、雌激素水平与GC干预持续时间之间的相关性。
DXM组在所有时间点的体重、肾上腺重量和子宫重量均显著低于基线组和对照组(P < 0.05)。DXM组PINP和β-CTX水平缓慢升高,与基线组和对照组相比,12周时差异有统计学意义(P < 0.05),但4周和8周时差异无统计学意义(P > 0.05)。DXM组在所有时间点的雌激素水平均显著低于基线组和对照组(P < 0.05)。GC干预后,DXM组腰椎和股骨的BMD、BMC和BA在所有时间点均显著低于对照组(P < 0.05)。DXM组L2和股骨转子区的骨量丢失在所有感兴趣区域(ROI)中最低。DXM组4周时腰椎的BMC和BA以及股骨干的BA显著低于基线组(P < 0.05)。但在所有时间点,DXM组与基线组相比,其他腰椎和股骨ROI的BMD、BMC和BA差异无统计学意义(P > 0.05)。GC干预后,腰椎和股骨的BMD与PINP和β-CTX呈负相关(P < 0.05),与雌激素水平呈正相关(P < 0.05)。
GC干预后早期骨量迅速下降,随后随时间维持在低水平,骨转换标志物水平呈渐进性升高,雌激素水平呈下降趋势。此外,体重、骨转换标志物水平和雌激素与骨量变化相关。