活性维生素D对卵巢切除大鼠骨转换与骨质量的影响

EFFECTS OF 1αOHD 3 ON THE BONE TURNOVER AND QUALITY IN OVARIECTOMIZED RATS

目的 研究１αＯＨＤ３ 对骨质疏松的预防治疗效果和作用机理。 方法 将４０ 只雌性Ｗｉｓｔａｒ大鼠分为４组，以切除卵巢大鼠为模型，分别用０．０４ μｇ／ｋｇ·ｄ 和０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 灌胃给药１２周。测定各组大鼠的血、尿生化指标，骨密度，生物力学和形态计量学等参数，以及骨粘连蛋白基因的表达水平。 结果 切除卵巢大鼠骨吸收和骨形成显著加强，骨密度明显降低，骨小梁结构恶化，骨生物力学性质显著降低。１αＯＨＤ３ 使大鼠骨量恢复，骨密度提高，骨小梁相对体积（ＴＢＶ）增大，并使骨生物力学性质明显提高。０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 对骨生物力学的效果优于０．０４ μｇ／ｋｇ·ｄ １αＯＨＤ３ 的给药量。不同浓度１αＯＨＤ３ 对骨形成与骨吸收的作用不同：０．５ μｇ／ｋｇ·ｄ１αＯＨＤ３ 明显抑制骨转换；０．０４ μｇ／ｋｇ·ｄ １αＯＨＤ３ 则促进骨转换。１αＯＨＤ３ 的浓度对骨的矿化速率无显著影响。大鼠去卵巢后，骨粘连蛋白（ｏｓｔｅｏｎｅｃｔｉｎ， ＯＮ）ｍ ＲＮＡ表达水平降低，０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 处理可恢复并促进ＯＮｍ ＲＮＡ 表达。 结论 １αＯＨＤ３ 有明显增加骨密度和骨强度的作用。

Objective\ To investigate mechanisms of prevention and treatment of osteoporosis using 1αOHD 3. Methods\ Forty female Wistar rats(3 months old) were divided into two groups, sham operated(sham) and ovariectomized. 1αOHD 3 was given orally at the dose of 0 5 μg/kg·d and 0 04 μg/kg·d for 12 weeks, respectively. At the end of the experiments, serum levels of bone gel protein(BGP) and estrogen were determined by ELISA, serum alkaline phosphatase(ALP), calcium(Ca),phosphatase, tartrate\|resistant acid phosphatase(TRAP) and urinary creatinine (Cr), hydroxyproline(HOP) and urinary Ca were determined by chemical method. Mechanical parameters for femur fracture in a three point bending test, histomorphometric parameters and the expression of osteonectin(ON) mRNA were measured.Results Ovariectomy increased bone formation and resorption and decreased bone mineral density(BMD) of the femur and the 4th lumbar vertebra and decreased the mechanical parameters of trabecular significantly. After administration of 1αOHD 3, the bone loss decreased while BMD, BV/TV(trabecular bone volume) and mechanical parameters increased. There was a more effective improvement of mechanical parameters in 0 5 μg/kg·d 1αOHD 3 group than that in 0 04 μg/kg·d 1αOHD 3 group. The former group inhibited bone turnover significantly, while the later group significantly stimulated bone turnover. There was no significant effect on mineral apposition rate(MAR) after treatment. The expression of ON mRNA increased after 0 04 μg/kg·d 1αOHD 3 treatment.Conclusion 1αOHD 3 could significantly improve the BMD and bone strength. The former group inhibited bone turnover significantly, while the later group significantly stimulated bone turnover.