异补骨脂素对模拟微重力引起的骨质流失的防治作用  

Therapeutic effect of isopsoralen on bone loss induced by simulated microgravity

作　　者：唐汉琴 李亮 轩莹莹 杨玉田 武艺 庞永杰 马智慧 高玉海 陈克明 TANG Hanqin;LI Liang;XUAN Yingying;YANG Yutian;WU Yi;PANG Yongjie;MA Zhihui;GAO Yuhai;CHEN Keming(College of Life Sciences and Engineering,Lanzhou University of Technology,Lanzhou 730050,China;Basic Medicine Laboratory of 940th Hospital of Joint Logistics Support Force,Lanzhou 730050,China)

机构地区：[1]兰州理工大学生命科学与工程学院,甘肃兰州730050 [2]联勤保障部队第九四○医院基础医学实验室,甘肃兰州730050

出　　处：《中国骨质疏松杂志》2024年第11期1612-1616,1632,共6页Chinese Journal of Osteoporosis

基　　金：中国人民解放军联勤保障部队第九四〇医院实验室培育项目(2021yxky081);甘肃省自然科学基金(22JR11RA013);兰州市科技计划项目(2023-1-8)。

摘　　要：目的研究异补骨脂素对模拟微重力导致小鼠骨质流失的治疗作用。方法将C57BL/6J小鼠随机分为5组:地面对照组(CON)、尾吊组(HU)、低剂量给药组(ISO-L)、中剂量给药组(ISO-M)、高剂量给药组(ISO-H),每组12只。给药21 d后,处死所有小鼠,取五脏、血清、股骨、胫骨,用于组织病理学检测、Mirco-CT成像分析、血清指标检测、股骨骨组织蛋白分析以及碱性磷酸酶阳性克隆染色。结果与CON组相比,HU组骨密度(bone mineral density,BMD)和骨小梁厚度(Tb.Th)均呈显著降低趋势(P<0.01),骨体积分数(BS/TV)、骨表面积密度(BV/TV%)明显降低(P<0.05),骨小梁数量(Tb.N)下降,骨小梁分离度(Tb.Sp)升高;与HU组相比,尾吊给药后BMD、BV/TV%、Tb.Th、BS/TV均显著升高(P<0.05),Tb.N升高,Tb.Sp下降,均以高剂量组效果最佳。与CON组相比,HU组血清中骨钙素(OCN)下降(P<0.01),抗酒石酸酸性磷酸酶5b(TRACP-5b)浓度上升(P<0.01);尾吊时给予异补骨脂素,使OCN升高(P<0.01),TRACP-5降低(P<0.01)。与CON组相比,HU组的OPG蛋白表达量降低(P<0.05),RANKL蛋白表达量升高(P<0.05),与HU组相比,给予异补骨脂素后OPG、蛋白表达量升高,RANKL的蛋白表达量降低(P<0.05)。HU组所显示的蓝紫色碱性磷酸酶染液颗粒与地面对照组相比密度低,颜色浅,尾吊时加入异补骨脂素后蓝紫色碱性磷酸酶染液颗粒密度升高。结论异补骨脂素能促进模拟微重力状态下骨形成同时抑制骨吸收有效防治骨质的流失。Objective To study the therapeutic effect of isopsoralen on bone loss induced by simulated microgravity in mice.Methods C57BL/6J mice were randomly divided into 5 groups;ground control group(CON),tail suspension group(HU),low dose group(ISO-L),middle dose group(ISO-M)and high dose group(ISO-H),with 12 mice in each group.After 21 days of administration,all mice were sacrificed,and the five internal organs,serum,femur and tibia were taken for histopathological examination,Mirco-CT imaging analysis,serum index detection,femoral bone tissue protein analysis and alkaline phosphatase positive clone staining.Results Compared with CON group,bone mineral density(BMD)and trabecular thickness(Tb.Th)in HU group decreased significantly(P<0.01),bone volume fraction(BS/TV),bone surface area density(BV/TV%)decreased significantly(P<0.05),trabecular number(Tb.N)decreased,trabecular separation(Tb.Sp)increased;Compared with HU group,BMD,BV/TV%,Tb.Th,BS/TV increased significantly(P<0.05),Tb.N increased and Tb.Sp decreased after tail suspension administration,and the effect of high dose group was the best.Compared with CON,serum osteocalcin(OCN)in HU decreased(P<0.01),and the concentration of tartrate-resistant acid phosphatase 5b(TRACP 5b)increased(P<0.01);When isopsoralen was administered during tail suspension,OCN increased(P<0.01)and TRACP-5 decreased(P<0.01).Compared with CON group,OPG protein expression in HU group decreased(P<0.05)and RANKL protein expression increased(P<0.05).Compared with HU group,OPG and RANKL protein expression increased and RANKL protein expression decreased(P<0.05)after isopsoralen administration.Compared with the ground control groupthe density of blue-purple alkaline phosphatase particles in HU group was lower and lighter,and the density of blue-purple alkaline phosphatase particles increased after isopsoralen was added during tail hanging.Conclusion Isopsoralen can promote bone formation and inhibit bone resorption under simulated microgravity,and effectively prevent bone loss.

关 键 词：异补骨脂素 模拟微重力 骨质流失 

分 类 号：R965[医药卫生—药理学]