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蒙药沙棘防治绝经后骨质疏松症及对骨髓间充质干细胞 ER/AKT/ERK 通路的影响

Mongolian Medicine echinops prevented postmenopausal osteoporosis and induced ER/AKT/ERK pathway in BMSCs.

机构信息

School of Basic Medical Science, Nanjing University of Chinese Medicine.

Department of Traditional Chinese Medicine, Affiliated Hospital of Inner Mongolia Medical University.

出版信息

Biosci Trends. 2018 Jul 17;12(3):275-281. doi: 10.5582/bst.2018.01046. Epub 2018 May 22.

DOI:10.5582/bst.2018.01046
PMID:29794404
Abstract

Hormone replacement medicine such as traditional Chinese medicine has proven to be effective in decreasing the risk of osteoporosis. Mongolian medicine echinops prevents osteoporosis, but its mechanism remains unclear. In this study, we explored the mechanism underlying echinops prevents and treats postmenopausal osteoporosis. Osteoporosis model was established by ovariectomy in rats. Rats were treated to Echinops (16.26, 32.5, or 65 mg/kg/day) by oral gavage for 3 months. Bone mineral density (BMD) was detected by micro-CT detection of left proximal medial metaphyseal tibia. Hematoxylin and eosin (H&E) and toluidine blue O staining were also performed. Serum levels of E2, ALP and testosterone were examined. Bone marrow-derived bone marrow stem cells (BMSCs) were isolated and treated with echinops-containing serum. Estrogen receptors (ER) including ERα and ERβ in bone specimens and BMSCs were detected by qRT-PCR. Cell viability and colon formation of BMSCs were detected. Expressions of ERα, ERβ, AKT, p-AKT, ERK, and p-ERK in BMSCs were detected by western blot. Results showed that echinops significantly increased trabecular interconnectivity, thickness of trabeculae, and connection of trabecula. Echinops significantly increased BMD and E2, but significantly reduced ALP and testosterone in dose-dependent manners. Echinops induced ERα and ERβ in both bone specimens and BMSCs. Echinops enhanced cell viability and ability of colony formation of BMSCs, and increased ERα, ERβ, p-AKT, and p-ERK. Thus, Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERα, ERβ, p-AKT, and P-ERK in BMSCs. These results provide experimental basis for clinical prevention and treatment of postmenopausal osteoporosis by echniops.

摘要

激素替代疗法如中药已被证明能有效降低骨质疏松症的风险。蒙药沙葱可预防骨质疏松症,但作用机制尚不清楚。本研究旨在探讨沙葱防治绝经后骨质疏松症的作用机制。通过卵巢切除术建立大鼠骨质疏松模型。大鼠经口灌胃给予沙葱(16.26、32.5 或 65mg/kg/天)3 个月。通过左侧胫骨近端内侧干骺端的 micro-CT 检测来检测骨矿物质密度(BMD)。还进行了苏木精和伊红(H&E)以及甲苯胺蓝 O 染色。检测血清 E2、碱性磷酸酶(ALP)和睾酮水平。分离骨髓源性骨髓基质细胞(BMSCs),并用含沙葱的血清处理。通过 qRT-PCR 检测骨标本和 BMSCs 中的雌激素受体(ER),包括 ERα和 ERβ。检测 BMSCs 的细胞活力和集落形成。通过 Western blot 检测 BMSCs 中 ERα、ERβ、AKT、p-AKT、ERK 和 p-ERK 的表达。结果表明,沙葱显著增加了小梁的连通性、小梁的厚度和小梁的连接。沙葱呈剂量依赖性地显著增加 BMD 和 E2,同时显著降低 ALP 和睾酮。沙葱诱导骨标本和 BMSCs 中 ERα和 ERβ的表达。沙葱增强了 BMSCs 的细胞活力和集落形成能力,并增加了 ERα、ERβ、p-AKT 和 p-ERK。因此,蒙药沙葱可减少骨丢失,延缓骨质疏松症的发生和发展,并增加 BMSCs 中的 ERα、ERβ、p-AKT 和 p-ERK。这些结果为临床预防和治疗绝经后骨质疏松症提供了实验依据。

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