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齐墩果酸通过调节SIRT1/FOXO1信号通路并抑制氧化应激来改善高脂饮食诱导的小鼠骨质疏松症。

Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress.

作者信息

Chen Xiaosi, Han Dengpeng, Liu Tianfeng, Huang Chengshuo, Hu Zibing, Tan Xiaoyan, Wu Shaoke

机构信息

International and Special Medical Service ward, Affiliated Hospital of Guangdong Medical University, Zhanjiang City, Guangdong Province, China.

Department of Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang City, Guangdong Province, China.

出版信息

Histol Histopathol. 2022 Aug;37(8):769-777. doi: 10.14670/HH-18-446. Epub 2022 Mar 1.

DOI:10.14670/HH-18-446
PMID:35229281
Abstract

Asiatic acid can attenuate osteoporosis through suppressing adipogenic differentiation and osteoclastic differentiation. Oxidative stress enhances osteoclastic differentiation but represses osteogenic differentiation to promote osteoporosis. However, the role and mechanism of asiatic acid in osteoporosis have not been reported. Firstly, mice were fed with high-fat-diet (HFD) with or without asiatic acid for 16 weeks. Data from an automatic biochemical analyzer showed that HFD induced down-regulation of high-density lipoprotein (HDL) and an increase of serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL). However, asiatic acid administration attenuated the decrease of HDL and increase of serum TG, TC and LDL in osteoporotic mice. Secondly, HFD induced high levels of malondialdehyde (MDA) and reactive oxygen species (ROS), low levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in osteoporotic mice. However, the levels of MDA, ROS, SOD and GSH-Px in osteoporotic mice were reversed by asiatic acid administration. (this section is unclear and requires revision) Asiatic acid administration reduced expression of c-telopeptide of type 1 collagen (CTX-1), enhanced alkaline phosphatase (ALP) and procollagen type 1 N-terminal propeptide (P1NP) in HFD-induced osteoporotic mice. (this section is unclear and requires revision) Thirdly, asiatic acid promoted calcium deposition in bone marrow cells and osteogenic differentiation in osteoporotic mice, but decreased ALP in bone marrow cells. Lastly, asiatic acid enhanced SIRT1 and nuclear FOXO1 (Nu-FOXO1) expression, while it reduced Acetyl FOXO1 (Ac-FOXO1) in osteoporotic mice. In conclusion, asiatic acid might inhibit oxidative stress and promote osteogenic differentiation through activating SIRT1/FOXO1 to attenuate HFD-induced osteoporosis in mice.

摘要

齐墩果酸可通过抑制成脂分化和破骨细胞分化来减轻骨质疏松症。氧化应激增强破骨细胞分化,但抑制成骨细胞分化以促进骨质疏松症。然而,齐墩果酸在骨质疏松症中的作用和机制尚未见报道。首先,将小鼠分为高脂饮食组(HFD),高脂饮食添加齐墩果酸组,喂养16周。自动生化分析仪数据显示,高脂饮食导致高密度脂蛋白(HDL)下调,甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白(LDL)血清水平升高。然而,给予齐墩果酸可减轻骨质疏松小鼠HDL的降低以及血清TG、TC和LDL的升高。其次,高脂饮食诱导骨质疏松小鼠丙二醛(MDA)和活性氧(ROS)水平升高,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平降低。然而,给予齐墩果酸可逆转骨质疏松小鼠的MDA、ROS、SOD和GSH-Px水平。(此部分不清楚,需要修订)给予齐墩果酸可降低高脂饮食诱导的骨质疏松小鼠中I型胶原C端肽(CTX-1)的表达,增强碱性磷酸酶(ALP)和I型前胶原N端前肽(P1NP)的表达。(此部分不清楚,需要修订)第三,齐墩果酸促进骨质疏松小鼠骨髓细胞中的钙沉积和成骨分化,但降低骨髓细胞中的ALP。最后,齐墩果酸增强骨质疏松小鼠中SIRT1和核FOXO1(Nu-FOXO1)的表达,同时降低乙酰化FOXO1(Ac-FOXO1)的表达。总之,齐墩果酸可能通过激活SIRT1/FOXO1抑制氧化应激并促进成骨分化,从而减轻高脂饮食诱导的小鼠骨质疏松症。

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