胎鼠长骨培养模型用于雌激素衍生物抗骨质疏松活性初步筛选

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目的 为对抗骨质疏松症化合物进行初步药理活性筛选寻找快捷、方便、经济的工具。 方法 取 16天胎龄的胎鼠尺骨 ,置于含BGJ培养基的培养瓶中 ,分别加入待测雌酚酮、骨靶向新化合物四环素 哌嗪雌酚酮 (XW6 30 )及其衍生物四环素 (2 羧酸酯 ) 哌嗪雌酚酮 (ZWI 1) ,通入CO2 、N2 和O2 混合气体 ,密闭后在旋转装置上培养 48h ,测量骨干长和骨总长 ,石蜡包埋切片后进行HE染色 ,光镜下计数破骨细胞和肥大软骨细胞。 结果 待测化合物浓度为 10 -7mol/L时 ,与对照组骨干长〔(1 2 2± 0 0 8)mm〕、骨总长〔(3 5 4± 0 0 7)mm〕、破骨细胞〔(12 3± 1 5 )个〕及肥大软骨细胞〔(10 0±1 0 )个〕相比 ,雌酚酮组、XW6 30组和ZWI 1组骨干长依次分别增至 (1 39± 0 0 9)mm、(1 46± 0 0 8)mm和 (1 49± 0 0 6 )mm(均为P <0 0 1)。骨总长分别增至 (3 76± 0 13)mm(P <0 0 5 )、(3 77± 0 2 2 )mm(P <0 0 5 )和 (3 90± 0 12 )mm(P <0 0 1)。破骨细胞分别减至 (5 3± 0 6 )个、(6 0± 1 6 )个和 (5 7±0 6 )个 (均为P <0 0 1)。肥大软骨细胞分别增至 (15 3± 1 5 )个 (P <0 0 1)、(14 2± 1 3)个 (P <0 0 5 )和 (15 6± 1 3)个 (P <0 0 1)。 结论 用该模型可同时观察到化合物对骨吸收 Aims To find a quick, convenient and economical tool for screening preliminary pharmacological activity of compounds against osteoporosis. Methods Twenty-four-day-old fetal rat ulnar rats were placed in culture flasks containing BGJ medium, and the testosterone was added separately. The bone-targeting new compound tetracycline piperazine estrone (XW6 30) and its derivative tetracycline (2 carboxylate) piperazine estrone (ZWI 1) was introduced into the mixed gas of CO2, N2 and O2. After sealing, the mixture was incubated on a rotating device for 48 hours. Total length and total length of the bone were measured. Paraffin embedded sections were stained with HE Under light microscope, counted osteoclasts and hypertrophic chondrocytes. Results When the concentration of test compound was 10 -7 mol / L, the total length of bone ([(122 ± 0 0 8) mm], total length of bone [(345 ± 0 0 7) mm), osteoclast (12 3 ± 1 5) and hypertrophic chondrocytes 〔(100 ± 1 0)〕, the skeletal length of estrone group, XW6 30 group and ZWI 1 group increased to (1 39 ± 0 0 9 mm, (1 46 ± 0 0 8) mm and (1 49 ± 0 0 6) mm respectively (all P 0 01). Total bone length increased to (3 76 ± 0 13) mm (3 77 ± 0 2 2) mm (P 0 05) and (3 90 ± 0 12) mm respectively (P 0 0 5) 0 1). The numbers of osteoclasts decreased to (53 ± 0 6), (60 ± 1 6) and (57 ± 0 6), respectively (all P <0.01). The number of hypertrophic chondrocytes increased to (15 3 ± 1 5), (14 2 ± 1 3) (P 0 05) and (15 6 ± 1 3) 0 1). Conclusions Compounds can be observed for bone resorption simultaneously with this model
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