摘要
目的探讨了BX-912对脂多糖(LPS)诱导的小鼠颅骨骨溶解症状的影响。方法体外实验:取C57BL/6小鼠全骨髓细胞,用巨噬细胞集落刺激因子(M-CSF)刺激分化成小鼠骨髓源巨噬细胞(BMMs),随后使用不同浓度的BX-912(0、0.078、0.156、0.312、0.625、1.25、2.5、5、10、20μmol/L)干预,通过Cell Counting Kit-8(CCK-8)检测BX-912对BMMs活性的影响。在M-CSF和RANKL诱导下使用0.312μmol/L浓度的BX-912干预破骨细胞分化,抗酒石酸酸性磷酸酶染色(TRAP染色)确定破骨细胞数目。体内实验:将30只6周龄的C57BL/6雄性小鼠随机分为3组,每组10只,分别为:PBS组、LPS组、BX-912治疗组。每隔一天注射一次药物,28 d后处死小鼠,分离颅骨并用4%多聚甲醛固定用于micro-CT扫描和组织学染色分析。结果 (1)与对照组相比,BX-912浓度在0.312μmol/L及以下时对BMMs活性无明显影响(P> 0.05);0.312μmol/L浓度BX-912可以明显抑制破骨细胞生成。(2)与LPS组相比,BX-912可以明显提高骨体积分数(BV/TV)、骨小梁数量(Tb.N),降低骨小梁分离度(Tb.Sp)。结论 BX-912可以改善LPS诱导的小鼠颅骨骨溶解的症状,抑制颅骨骨重吸收,有潜在的治疗骨质疏松症的效果。
Objective To investigate the effect of BX-912 on lipopolysaccharide(LPS) induced murine calvaria osteolysis mouse model. Methods In vitro experiments:bone marrow cells from C57BL/6 mouse were harvested and differentiated into bone marrow derived macrophages(BMMs) by macrophage colony stimulating factor(M-CSF). The effect of BX-912 on the activity of BMMs was determined by Cell Counting Kit 8(CCK-8) in different concentrations of BX-912( 0, 0.078, 0.156, 0.312, 0.625, 1.25, 2.5, 5, 10, 20 μmol/L). Osteoclast differentiation was induced by M-CSF and RANKL induction using a concentration of 0.312 μmol/L of BX-912, and the number of osteoclasts was determined by tartrate resistant acid phosphatase staining(TRAP staining). In vivo experiments:30 C57BL/6 male mice(6 weeks old) were randomly divided into 3 groups(10/group): PBS group,LPS group and BX-912 treatment group. The drug was injected every other day,and the mice were sacrificed 28 days later. The calvaria was dissected and fixed with 4% paraformaldehyde,and analyzed by micro-CT scanning and histological staining. Results (1)Compared with control group,there was no significant effect of BX-912on BMMs activity at 0.312 μmol/L or below concentration(P > 0.05). At 0.312 μmol/L concentration,BX-912 could significantly inhibit osteoclastogenesis.(2) Compared with LPS group,BX-912 could significantly increase the calvarial bone volume fraction(BV/TV), trabecular bone number(T b.N), and reduce trabecular bone separation(Tb.Sp). Conclusion BX-912 can improve the symptoms of osteoporosis, and inhibit the reabsorption of calvarial bone in LPS induced mouse model. BX-912 may have potential to treat osteoporosis.
作者
高云兵
岑忠喜
黄建华
邓贵营
何基琛
曾高峰
宗少晖
GAO Yunbing;CEN Zhongxi;HUANG Jianhua;DENG Guiying;HE Jichen;ZENG Gaofeng;ZONG Shaohui(Department of Spine Surgery,First Affiliated Hospital of Guangxi Medical University,Nanning 530000,China)
出处
《实用医学杂志》
CAS
北大核心
2019年第10期1540-1544,共5页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号:81860402)
广西高等学校高水平创新团队及卓越学者计划项目
广西自然科学基金项目(编号:2017GXNSFAA198073)
