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基质金属蛋白酶-9、RANKL/OPG 系统与绝经后骨质疏松症去卵巢大鼠模型心血管危险因素的相互作用。

The cross-talk between matrix metalloproteinase-9, RANKL/OPG system and cardiovascular risk factors in ovariectomized rat model of postmenopausal osteoporosis.

机构信息

Faculty of Medicine, Physiology Department, Cairo University, Giza, Egypt.

Faculty of Medicine, Histology and Cell Biology Department, Cairo University, Giza, Egypt.

出版信息

PLoS One. 2021 Oct 5;16(10):e0258254. doi: 10.1371/journal.pone.0258254. eCollection 2021.

Abstract

Epidemiology and pathogenesis of cardiovascular diseases (CVD) and osteoporosis are strikingly overlapping. This study presents matrix metalloproteinase-9 (MMP-9), as a simple molecular link more consistently associated with the pathophysiology of both osteoporosis and CVD risk factors. 40 adult female rats were randomly distributed into 4 groups [control sham-operated, untreated osteoporosis, carvedilol-treated osteoporosis and alendronate-treated osteoporosis]. After 8 weeks, blood samples were collected to estimate Lipid profile (Total cholesterol, HDL, Triglycerides), inflammatory markers (IL-6, TNF alpha, CRP and NO), and Bone turnover markers (BTM) (Alkaline phosphatase, osteocalcin and pyridinoline). The tibias were dissected to estimate MMP-9 and NF-kB gene expression, OPG, RANKL levels and for histological examination. Induction of osteoporosis resulted in a significant elevation in BTM, inflammatory markers and dyslipidemia. MMP-9 was significantly elevated and positively correlated with BTM, inflammation and dyslipidemia markers. Carvedilol and alendronate exerted a bone preservative role and attenuated dyslipidaemia and inflammation in accordance with their respective effect on MMP-9.

摘要

心血管疾病 (CVD) 和骨质疏松症的流行病学和发病机制惊人地重叠。本研究提出基质金属蛋白酶-9 (MMP-9),作为一个与骨质疏松症和 CVD 危险因素的病理生理学更一致相关的简单分子联系。40 只成年雌性大鼠被随机分为 4 组 [对照组假手术、未治疗骨质疏松症、卡维地洛治疗骨质疏松症和阿仑膦酸钠治疗骨质疏松症]。8 周后,采集血样以估计血脂谱(总胆固醇、HDL、甘油三酯)、炎症标志物(IL-6、TNF alpha、CRP 和 NO)和骨转换标志物(BTM)(碱性磷酸酶、骨钙素和吡啶啉)。解剖胫骨以估计 MMP-9 和 NF-kB 基因表达、OPG、RANKL 水平并进行组织学检查。骨质疏松症的诱导导致 BTM、炎症标志物和血脂异常显著升高。MMP-9 显著升高,并与 BTM、炎症和血脂异常标志物呈正相关。卡维地洛和阿仑膦酸钠具有骨保护作用,并根据它们对 MMP-9 的各自作用减轻血脂异常和炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd37/8491879/8ecbcb8e7390/pone.0258254.g001.jpg

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