尼尔雌醇对去势雌性大鼠1,25双羟维生素D水平的影响

 目的 研究卵巢摘除（ovariectomy，OVX）后大鼠血清25(OH)D、1,25双羟维生素D［1,25(OH)2D］水平和骨表型的变化及雌激素干预效果。方法 采用6月龄SD雌性大鼠双侧卵巢摘除术建立去势骨质疏松模型并随机分为去势模型组（OVX组）和去势后雌激素干预组（OVX-E组），另设假手术对照组（SHAM组），每组10只。术后5周OVX-E组开始灌服尼尔雌醇（1 mg/kg，2次/周），其他组灌服饮用水作为对照，均给药13周。采用酶免法（EIA）检测血清25(OH)D和1,25(OH)2D水平，用体积骨密度（volume bone mineral density，vBMD）和骨小梁面积（BV/TV）等指标进行骨表型分析。结果 OVX组血清25(OH)D水平保持稳定，与SHAM组比较差异无统计学意义。去势后1,25(OH)2D水平显著升高，OVX组为63.1 pmol/L，较SHAM组的38.5 pmol/L增加了64%（P<0.001）。OVX大鼠骨密度降低，较SHAM组分别减少9.5%（股骨，P<0.001）和9.8%（腰椎，P<0.001）。同时出现骨小梁面积减少和尿吡啶酚增加（58.7%，P<0.05）等骨质疏松表型。口服雌激素后，血清1,25(OH)2D水平较OVX组明显下降60.8% （P<0.001），甚至低于SHAM组（P<0.01），同时延缓骨丢失和改善骨微结构。结论 去势影响大鼠维生素D（vitamin D，VD）代谢，致血清1,25(OH)2D水平明显升高，小剂量雌激素对VD代谢改变和骨丢失具有显著纠正作用。

Changes of 1,25 dihydroxyvitamin D levels in ovariectomy female rats after Nilestriol treatment

Objective To study the changes of renal vitamin D metabolism and skeleton phenotypes in ovariectomized rats and effects of estrogen treatment. Methods Female SD rats (n=30) were randomly divided into 3 groups (n=10 for each). Bilateral ovariectomy for ovariectomy (OVX) and OVX-estrogen (OVX-E) groups, and sham surgery for SHAM group were performed at 6 month of age respectively. Meanwhile, estrogen (1 mg/kg Nilestriol in 2 mL drink water) in OVX-E group was administered twice a week by gavages from 6 to 18 weeks after operation. Same volume of drink water was used as the control for OVX and SHAM groups. The serum vitamin D levels, calcium and phosphate, and skeleton phenotypes were investigated at the middle or end of experiments. Results The serum 1,25(OH)2D level in OVX rats was 63.1 pmol/L, increased by 64% (P<0.001) compared with 38.5 pmol/L in SHAM. The high 1,25(OH)2D level was back down to 24.7 pmol/L by estrogen treatment in OVX-E (-60.8% versus OVX, P<0.001), which was lower than that in SHAM (P<0.01). The osteoporotic phenotypes in OVX rats were showed by the decrease (-9.5% in femur, P<0.001 and -9.8% in lumbar, P<0.001) of volume bone mineral density (vBMD), and the decrease of bone volume as determined by histomorphometry analysis. Bone resorption was activated after ovariectomy as showed by the increased urine PyD excretion (58.7%, P<0.05). Meanwhile, the calcium levels in serum and urine of OVX rats were lower than that in SHAM. The skeleton phenotypes were improved by Nilestriol treatment showed by increased vBMD and bone volume, increased serum calcium and decreased urine PyD excretion, while the urine Ca excretion still kept in lower level (-60%, versus SHAM, P<0.01). Conclusions The serum 1,25(OH)2D level was increased in ovariectomized osteoporotic rats, which was fell down by estrogen treatment along with improved bone quality and structure.