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目的探讨不同剂量糖皮质激素(GC)对大鼠骨量及骨代谢的影响,以及比较GC诱导骨质疏松模型(GICP模型)与卵巢摘除骨质疏松模型(0VX模型)对大鼠骨量及骨代谢影响的区别。方法 75只4个月龄雌性SD大鼠。随机分成五组,A组为正常对照组(Sham组,生理盐水灌胃);B组为低剂量GC组(泼尼松龙每天2.5 mg/kg)灌胃;C组为中剂量GC组(泼尼松龙每天5 mg/kg灌胃);D组为高剂量GC组(泼尼松龙每天10 mg/kg灌胃);E组为卵巢切除组(OVX组)。每天1次,GC组连续灌胃12周。分别于灌胃/去势后第4、8、12周从每组中各随机抽出5只SD大鼠,处死。取股骨干骺端进行不脱钙骨制片;利用显微CT扫描大鼠腰1段;利用酶联免疫吸附测定法(Elisa)检测静脉血中TRACP、G-ALP、BGP及尿液中DPD。结果 (1)各实验组4周后骨小梁排列渐稀疏,数目开始减少,小梁明显变细,间距加宽。随着给药时间的延长,改变更加明显;(2)骨密度检测:与对照组相比,GC低剂量组骨流失从给药后第8周开始明显(P<0.05),而GC中剂量和高剂量组骨流失从给药后4周就开始显现(P<0.05)。中剂量组与高剂量组各时间段差异均无统计学意义(P>0.05);与中等剂量和高等剂量相比,去势组第4周骨量流失差异有统计学意义(P<0.05),第8、12周差异无统计学意义(P>0.05)。(3)骨代谢生化指标的测定结果 :灌胃及摘除卵巢4周后,C组、D组、E组骨形成标记物(G-ALP、BGP)、骨吸收标记物(TRACP、DPD)与正常对照组差异有统计学意义(P<0.05)。结论 (1)大鼠骨量的流失可随着糖皮质激素剂量的增加而增加(呈浓度依赖性)。(2)在OVX模型中,骨重建能力上升,而在GIOP模型中,骨重建能力下降。
Objective To investigate the effect of different doses of glucocorticoid (GC) on bone mass and bone metabolism in rats and to compare the effects of GC-induced osteoporosis (GICP) model and ovariectomized osteoporosis model (OVX model) on bone mass and The difference between bone metabolism. Methods 75 4-month-old female SD rats. Group A was normal control group (Sham group, saline); group B was low-dose GC group (prednisolone 2.5 mg / kg daily); Group C was medium dose GC group Prednisolone 5 mg / kg per day); group D was high-dose GC (prednisolone 10 mg / kg per day), and group E was ovariectomized (OVX). Once a day, the GC group was given gavage for 12 weeks. At the 4th, 8th and 12th week after gavage / castration, 5 SD rats were randomly selected from each group and sacrificed. The metaphyseal femoral metaphyseal bone fragments were prepared for non-decalcification. The lumbar 1-segment of rat was scanned by micro-CT. The levels of TRACP, G-ALP, BGP and urine DPP were detected by Elisa . Results (1) After 4 weeks of each experimental group, the arrangement of trabeculae was gradually sparse, the number began to decrease, the trabeculae conspicuously thinned and the spacing widened. (2) Bone mineral density test: Compared with the control group, the bone loss in the low-dose GC group began to be significant at the 8th week (P <0.05), while the median dose of GC In the high-dose group, bone loss started to manifest 4 weeks after administration (P <0.05). There was no significant difference between the middle dose group and the high dose group in each time period (P> 0.05). Compared with the medium dose and the high dose, there was significant difference in the amount of bone loss in the castrated group at the fourth week (P <0.05) There was no significant difference between the 8th and 12th weeks (P> 0.05). (3) The results of biochemical analysis of bone metabolism: After 4 weeks of gavage and ovariectomy, the bone formation markers (G-ALP, BGP), bone resorption markers (TRACP, DPD) The difference between the normal control group was statistically significant (P <0.05). Conclusions (1) The loss of bone mass in rats may increase with dose of glucocorticoid (in a dose-dependent manner). (2) In the OVX model, the capacity of bone remodeling increased, while in the GIOP model, the capacity of bone remodeling decreased.