多肽HAIYPRH对去卵巢骨质疏松小鼠的影响

Effects of the Polypeptide HAIYPRH on Ovariectomized Osteoporotic Mice

关键词:  多肽  骨质疏松  骨密度  骨微结构

Key words:  peptide  osteoporosis  bone mineral density  bone microstructure

摘要:

摘要：目的 研究多肽HAIYPRH（HAI）对去卵巢（ovariectomized，OVX）骨质疏松（osteoporosis，OP）小鼠的影响。方法 将30只8周龄的SPF级雌性C57BL/6J小鼠随机分为假手术组、模型组、苯甲酸雌二醇组（0.2 mg·kg-1）、HAI低剂量组（60 mg·kg-1）、HAI高剂量组（120 mg·kg-1），每组6只。除假手术组外，其余组行双侧卵巢切除术构建OP模型。每2 d腹腔注射给药1次，持续3个月。通过检测骨密度（bone mineral density，BMD）、骨矿物质含量（bone mineral content，BMC）、骨微结构参数及血清代谢指标，结合组织形态学观察及免疫组化染色，评估HAI对OP小鼠的骨保护作用。结果 与假手术组比较，模型组BMD降低，骨微结构受损，骨形成标志物水平降低，表明造模成功。与模型组相比，HAI能显著改善股骨骨微结构，提高BMD，增加骨形成标志物骨碱性磷酸酶（bone alkaline phosphatase，BALP）、Ⅰ型前胶原氨基端前肽（procollagen type I N propeptide，PINP）、骨钙素（osteocalcin，BGP）水平，同时上调runt相关的转录因子2（runt-related transcription factor 2，RUNX2）和骨桥蛋白（osteopontin，OPN）蛋白表达。此外，HAI对小鼠主要脏器无不良影响。结论 HAI能促进OP小鼠骨形成，提高股骨BMD并改善股骨骨微架结构，从而达到防治OP的效果，本研究剂量下HAI对OP小鼠无不良影响，为后续开发为改善OP的相关产品提供了理论参考。

Abstract:

ABSTRACT: OBJECTIVE To investigate the effect of the polypeptide HAIYPRH (HAI) on ovariectomized (OVX) mice with osteoporosis (OP). METHODS Thirty 8-week-old SPF-grade female C57BL/6J mice were randomly divided into a sham group, a model group, an estradiol benzoate group (0.2 mg·kg-1), and low-dose (60 mg·kg-1) and high-dose (120 mg·kg-1) HAI groups, with 6 mice in each group. Except for the sham group, the other groups underwent bilateral ovariectomy to establish the OP model. Drugs were administered intraperitoneally every 2 days for 3 months. Bone mineral density (BMD), bone mineral content (BMC), bone microstructural parameters, and serum metabolic indicators were measured, combined with histomorphological observations and immunohistochemical staining, to assess the bone-protective effects of HAI on OP mice. RESULTS Compared with the sham group, the model group exhibited decreased BMD, impaired bone microstructure, and reduced levels of bone formation markers, indicating successful modeling. Compared with the model group, HAI significantly improved femoral bone microstructure, increased BMD, and elevated the levels of bone formation markers such as bone alkaline phosphatase (BALP), procollagen type I N-terminal propeptide (PINP), and osteocalcin (BGP). Additionally, HAI upregulated the protein expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN). Furthermore, HAI had no adverse effects on the major organs of the mice. CONCLUSION HAI can promote bone formation, increase femoral BMD, and improve femoral bone microarchitecture in OP mice, thereby achieving the effect of preventing and treating OP.