新型β-链蛋白结合药物SAHPA1治疗去卵巢小鼠骨质疏松

A novel β-catenin-binding drug SAHPA1 in treatment of osteoporosis in ovariectomized mice

目的评估新型β-链蛋白(β-catenin)结合药物SAHPA1在绝经后骨质疏松小鼠模型中的治疗效果。方法选取C57雌性小鼠作为实验对象。将实验动物分为3组,分别为假手术组、骨质疏松模型组(模型组)、骨质疏松模型治疗组(治疗组),每组5只小鼠。假手术组仅暴露卵巢后缝合切口;模型组和治疗组动物行双侧卵巢切除,建立去卵巢骨质疏松模型。治疗组在切除卵巢后即刻开始每日肌注β-catenin结合药物SAHPA1(10mg/kg),假手术组和模型组每日注射同剂量的生理盐水。8周后,利用骨组织切片H-E染色、micro-CT等方法观察小鼠股骨干骺端骨小梁形态并进行形态学计量分析,评估SAHPA1对去卵巢骨质疏松的治疗效果。结果与假手术组比较,模型组小鼠骨密度、骨小梁数量、骨小梁厚度均降低,差异有统计学意义(P<0.05)。经SAHPA1治疗后,小鼠骨密度和骨小梁数量增高(P<0.05),骨小梁厚度与模型组比较虽有一定提升但差异无统计学意义(P>0.05)。结论新型β-catenin结合药物SAHPA1对绝经后骨质疏松小鼠模型有一定治疗作用。

Objective To evaluate the therapeutic effect of novel β-catenin-binding drug SAHPA1 on postmenopausal osteoporosis animal models. Methods C57 female mice were selected and divided into 3 groups （n=5） ： Sham group, osteoporosis model group （OP group）, and osteoporosis model treatment group （Treat group）. The mice in the Sham group only underwent surgical incision exposing bilateral ovaries, while the mice in the OP and Treat groups underwent bilateral ovariectomy and the ovariectomized osteoporosis mouse models were established. Then the mice in the Treat group were immediately treated with SAHPA1 （10 mg/kg） by daily intramuscular injection, and those in the Sham and OP groups were injected with the same dose of saline daily. The morphology of trabecular bone in the femur metaphyseal bone in miee was observed and the morphometric analysis was performed by bone tissue sections with H-E staining and miero-CT. The therapeutic effect of SAHPA1 on osteoporosis in ovarieetomized mice models was also evaluated. Results The bone mineral density （BMD）, trabeeular bone number （Tb. N） and trabeeular bone thickness （Tb. Th） of mice in the OP group were significantly lower than those in the Sham group （P〈0. 05）. The BMD and Tb. N of mice in the Treat group were significantly higher than those in the OP group （P〈0. 05）, while there was no significant difference in Tb. Th between the two groups （P〉0. 05）. Conclusion The novel β-catenin-binding drug SAHPA1 has a certain therapeutic effect on postmenopausal mice with osteoporosis.