AN04-2治疗骨质疏松的成药性评价

目的考察AN04-2对骨质疏松的治疗作用和安全性,对其成药性进行评价。方法人成骨细胞hFOB1.19加入不同浓度的AN04-2处理7 d,检测碱性磷酸酶(ALP)的表达;野生型AB品系斑马鱼,以泼尼松诱导建立骨质疏松症模型,分别注射给予不同剂量的AN04-2处理,测定斑马鱼脊椎骨荧光强度;雌性SD大鼠行双侧卵巢切除手术(OVX),建立大鼠骨质疏松模型,给予不同剂量的AN04-2治疗12周,测量腰椎L5及右股骨的骨密度;SD大鼠单次静脉注射给予生理盐水及不同剂量的AN04-2,观察动物的急性毒性反应。结果0.3~10μmol/L浓度的AN04-2可显著促进人成骨细胞HFOB1.1的ALP的表达;剂量为15、50 ng/尾的AN04-2治疗可显著增加斑马鱼脊椎骨荧光强度(P<0.001);1周1次皮下注射不同剂量的AN04-2,OVX大鼠的第五腰椎和右股骨的BMD有升高的趋势,但差异无统计学意义(P>0.05)。大鼠单次静脉注射AN04-2高至100 mg/kg,未见明显不良反应。结论AN04-2体内外对骨质疏松均有一定的治疗作用,且安全性良好,具有较好的成药性。

The medicinal property of AN04-2 in the treatment of osteoporosis

Objective To investigate the therapeutic effect and safety of AN04-2 on osteoporosis,and to evaluate its medicinal property.Methods Human osteoblast hFOB1.19 cells were treated with different concentration of AN04-2 for 7 days.The expression of ALP was detected.The zebrafish model of osteoporosis was established by inducing with prednisone.Model zebrafish was injected with different doses of AN04-2.The fluorescence intensity of zebrafish vertebrae was analyzed and counted.Female SD rats were performed bilateral ovariectomy(OVX)to establish osteoporosis model.Different doses of AN04-2 were given on the second day after operation for 12 weeks.The BMD of L5 of lumbar vertebrae and the right femur were measured after treatment.The rats received saline and different doses of AN04-2 intravenously.The acute toxic reaction of the animals was observed.ResultsThe ALP expression of human osteoblasts HFOB1.1 at the concentration of 0.3-10μmol/L of AN04-2 was significantly promote.The fluorescence intensity of zebrafish spine increased significantly when treated with 15ng or 50ng/fish of AN04-2(P<0.001).BMD of the L5 lumbar vertebra and the right femur in the AN04-2 treatment group increased,but the difference was not statistically significant(P>0.05).AN04-2 was well tolerated following single intravenous dose up to 100 mg/kg in rats.Conclusion AN04-2 has a certain effect on osteoporosis in vitro and in vivo.The safety of AN04-2 is well.AN04-2 has a good medicinal property.