CAJ | 학술논문

目的采用地塞米松建立斑马鱼骨质疏松模型，筛选先导物G39及其结构类似物的抗骨质疏松活性。 　　方法斑马鱼 AB 系胚胎受精后6~72 h 浸于地塞米松溶液建模，受精后3 d分组给药直至受精后6 d，收集固定斑马鱼幼体；采用茜素红染色法显示成骨发育状况，显微拍照后以 G39为对照，进行斑马鱼头面骨成骨面积和骨矿化密度的半定量分析，比较六种2-乙酰苯并五元杂环类化合物潜在的抗骨质疏松活性。 　　结果 G395μg/ml 组对地塞米松导致的斑马鱼骨质疏松具有显著的改善作用，且实验结果与地塞米松大鼠模型具有一致性。以此筛选 G39衍生物体内活性，发现苯并呋喃衍生物410活性优于 G39。 　　结论地塞米松斑马鱼骨质疏松模型评价周期缩短、成本低，使抗骨质疏松药物体内活性批量筛选成为可能，为更快更准地发现抗骨质疏松候选药物打下坚实基础。通过本研究筛选得到了全新结构类型的抗骨质疏松化合物410，其活性较 G39更强，值得进一步研究。
목적채용지새미송건립반마어골질소송모형，사선선도물G39급기결구유사물적항골질소송활성。 　　방법반마어 AB 계배태수정후6~72 h 침우지새미송용액건모，수정후3 d분조급약직지수정후6 d，수집고정반마어유체；채용천소홍염색법현시성골발육상황，현미박조후이 G39위대조，진행반마어두면골성골면적화골광화밀도적반정량분석，비교륙충2-을선분병오원잡배류화합물잠재적항골질소송활성。 　　결과 G395μg/ml 조대지새미송도치적반마어골질소송구유현저적개선작용，차실험결과여지새미송대서모형구유일치성。이차사선 G39연생물체내활성，발현분병부남연생물410활성우우 G39。 　　결론지새미송반마어골질소송모형평개주기축단、성본저，사항골질소송약물체내활성비량사선성위가능，위경쾌경준지발현항골질소송후선약물타하견실기출。통과본연구사선득도료전신결구류형적항골질소송화합물410，기활성교 G39경강，치득진일보연구。
Objective To screen the anti-osteoporosis activities of lead compound G39 and its structural analogues using dexamethasone 6-72 hpf zebrafish model. Methods In groups, embryos from AB lines of 6 hpf zebrafish were incubated in dexamethasone solution for 72 h and drugs were then administered, respectively. Embryos were cultured till 6 dpf and then harvested followed by alizarin red staining, rehydration, decoloration, photomicrography, and analysis of staining results. Anti-osteoporosis activity screening experiments were carried out through the above steps in this dexamethasone zebrafish model. The experiments were divided into groups including wild type control, model control, model solvent control, and drug evaluation groups with various doses. Results The 5μg/ml G39 group showed significant activity in this dexamethasone zebrafish model, which is consistent with results from glucocorticoid rats model. Parallel screening of G39 derivatives was performed and it was discovered that benzofuran derivative 410 showed greater activity than G39 did. Conclusion Due to its shortened evaluation cycle and low cost, dexamethasone zebrafish model makes it possible to evaluate the activities of anti-osteoporosis drugs in large quantities in vivo, laying a solid foundation for the faster and more accurate discovery of anti-osteoporosis drugs. An anti-osteoporosis compound 410, which shows a whole new structure and a greater activity than G39 does, is screened out through this study, and is worthy of further investigation.