Effect of Small-molecule GLP- 1 Receptor Agonist in Ovariectomized Mice with Osteoporosis / 中国药房

ABSTRACT

OBJECTIVE：To ex plore the improvement effects of small-molecule glucagon-like peptide- 1 receptor（GLP-1R） agonists（6，7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline，DMB）on osteoporosis model mice. METHODS ：C57BL/ 6J mice were randomly divided into sham operation group ，model group ，positive control group （17β-estradiol，10 μg/kg）and DMB group （1 mg/kg），with 10 mice in each group. The sham operation group received bilateral laparotomy without ovariectomy ， and the other groups received bilateral ovariectomy to reproduce the osteoporosis model. At 4th week after operation ，sham operation group and model group were given constant volume of florence oil intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 8 weeks. After last medication ，Micro-CT was used to detect the femur microstructure ，bone mineral density （BMD），bone mineral content （BMC）and bone morphometric parameters [bone tissue volume fraction （BV/TV），trabecular thickness （Tb.Th），trabecular number （TB.N）and trabecular spacing （Tb.Sp）]. ELISA assay was used to detect the expression of bone formation indexes [bone specific alkaline phosphatase （BALP），osteoprotegerin（OPG）] and bone resorption indexes [tartrate resistant acid phosphatase （TRAP）and C-terminal cross-linked peptide of type Ⅰ collagen （CTX-Ⅰ）]. Three-point bending test was used to detect biomechanical parameters （maximum load ，stiffness，stress and Young ’s modulus）of femur of mice in each group. RESULTS ：In sham operation group ，trabeculae were numerous ，thick，complete in morphological structure ，well-organized and reticular ；bone Δ 基金项目：国家自然科学基金资助项目（No.81402931）；陕西省 重点研发计划项目（No.2017SF-261）；西安医学院 2016年博士科研启 microstructure and bone mass were normal. Compared with 动基金项目（No.2016DOC27） sham operation group ， the number of trabecular bone ＊讲师，博士。研究方向 ：分子药理学 。E-mail：zhouying209@ decreased，the thickness became thinner ，twisted or broken ， 163.com and the trabecular space increased ；the bone microstructure ·284· China Pharmacy 2021Vol. 32 No. 3 中国药房 2021年第32卷第3期 deteriorated and the bone m ass decreased ；BMD，BMC，BV/TV，Tb.Th，Tb.N and biomechanical parameters of femur were decreased significantly ，while Tb.Sp and serum levels of BLAP ，OPG，TRAP and CTX- Ⅰ were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ，the bone mass of positive control group and DMB group were increased ，while the number，thickness and shape of trabecular bone partially recovered ；BMD，BMC，BV/TV，Tb.Th，Tb.N and biomechanical parameters of femur were increased significantly （P＜0.05 or P＜0.01）；Tb.Sp，serum levels of BLAP and OPG were increased significantly （P＜0.01）， while the levels of TRAP and CTX- Ⅰ were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：DMB can improve osteoporosis by increasing bone mass ，improving bone microstructure ，increasing the expression of bone formation related indexes and biomechanical parameters and decreasing bone resorption related indexes.