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| 有氧运动通过激活SIRT1/FoxO1信号通路改善去卵巢骨质疏松小鼠的骨质流失 |
| Aerobic exercise ameliorates bone loss through activation of the SIRT1/FoxO1 signaling pathway in ovariectomized osteoporotic mice |
| 投稿时间：2023-11-15 修订日期：2024-02-26 |
| DOI： |
| 中文关键词: 有氧运动 骨质疏松症 卵巢切除术 氧化应激 骨代谢 SIRT1/FoxO1信号通路 |
| 英文关键词:aerobic exercise osteoporosis ovariectomy oxidative stress bone metabolism SIRT1/FoxO1 signaling pathway |
| 基金项目:山西森林康养体育人才培养模式及路径研究 GH-21162 |
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| 中文摘要: |
| 目的:本研究旨在探讨长期有氧运动对卵巢切除骨质疏松症小鼠骨质流失和氧化应激的影响,并初步探讨潜在的分子机制。方法:采用双侧卵巢切除法制备骨质疏松小鼠模型。将小鼠随机分为Sham组、OVX组(OVX组)、雌二醇组(E2组)、有氧运动组(AE组)、有氧运动+SIRT1抑制剂组(AE+EX527组),每组10只。E2组给予戊酸雌二醇1 mg/kg灌胃；AE组进行跑步训练；AE+EX527组除定期跑步训练外,给予SIRT1抑制剂EX527灌胃(5 mg/kg)；Sham组和OVX组每日给予等体积生理盐水。采用micro-CT测量小鼠股骨骨密度(BMD)、骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁分离度(Tb.Sp)。采用苏木精伊红染色观察股骨组织病理形态。采用酶联免疫吸附法测定骨代谢指标总碱性磷酸酶(ALP)、骨钙素(BGP)、I型胶原交联羧基末端区(CTx-I)和抗酒石酸性磷酸酶5 b(TRACP5b)的水平。使用二氢乙锭(DHE)染色检测骨组织活性氧(ROS)水平。采用相应试剂盒检测血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)的水平。采用蛋白免疫印迹分析股骨组织中沉默信息调节因子1(SIRT1)、叉头盒蛋白O1(FoxO1)和Ac- FoxO1蛋白表达。结果:与Sham组相比,OVX组小鼠BMD、Tb.Ar、Tb.N和Tb.Th,血清BGP、SOD和GSH-Px水平,以及股骨组织中SIRT1和FoxO1蛋白表达均明显降低,而Tb.Sp,血清ALP、TRACP5b、CTx-I和MDA水平,以及股骨组织ROS水平和Ac-FoxO1蛋白表达均明显升高(P＜0.05)。与OVX组相比,E2组和AE组BMD、Tb.Ar、Tb.N和Tb.Th,血清BGP、SOD和GSH-Px水平,以及股骨组织中SIRT1和FoxO1蛋白表达均明显升高,而Tb.Sp,血清ALP、TRACP5b、CTx-I和MDA水平,以及股骨组织ROS水平和Ac-FoxO1蛋白表达均明显降低(P＜0.05)。与AE组相比, AE+EX527组BMD、Tb.Ar、Tb.N和Tb.Th,血清BGP、SOD和GSH-Px水平,以及股骨组织中SIRT1和FoxO1蛋白表达均明显降低,而Tb.Sp,血清ALP、TRACP5b、CTx-I和MDA水平,以及股骨组织ROS水平和Ac-FoxO1蛋白表达均明显升高(P＜0.05)。结论:有氧运动可能通过激活SIRT1/FoxO1信号通路来抑制氧化应激,从而改善OVX小鼠的骨质流失。 |
| 英文摘要: |
| Objective: The aim of this study was to investigate the effects of long-term aerobic exercise on bone loss and oxidative stress in ovariectomized osteoporotic mice, and to preliminarily explore the potential molecular mechanisms. Methods Osteoporotic mouse models were prepared by bilateral ovariectomy. The mice were randomly divided into Sham group, OVX group (OVX group), estradiol group (E2 group), aerobic exercise group (AE group), and aerobic exercise+SIRT1 inhibitor group (AE+EX527 group), with 10 mice in each group. The E2 group was given estradiol valerate 1 mg/kg by gavage; The AE group was trained with running; The AE+EX527 group was given the SIRT1 inhibitor EX527 by gavage (5 mg/kg) in addition to regular running training; Sham and OVX groups were given equal volumes of saline daily. The bone mineral density (BMD), bone volume fraction (BV/TV), number of trabeculae (Tb.N), thickness of trabeculae (Tb.Th), and separation of trabeculae (Tb.Sp) were measured in the femur of mice using micro-CT. Hematoxylin eosin staining was used to observe the histopathological morphology of the femur. The levels of bone metabolism indexes total alkaline phosphatase (ALP), osteocalcin (BGP), cross-linked carboxy-terminal region of type I collagen (CTx-I), and tartrate-resistant acid phosphatase 5 b (TRACP5b) were measured by enzyme-linked immunosorbent assay. Bone tissue reactive oxygen species (ROS) levels were detected using dihydroethidium (DHE) staining. Serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected using the corresponding kits. Western blotting was used to analyze Silent Information Regulator 1 (SIRT1), Forkhead Box O1 (FoxO1) and Ac- FoxO1 protein expression in femoral tissues. Results: Compared with the Sham group, BMD, Tb.Ar, Tb.N and Tb.Th, serum levels of BGP, SOD and GSH-Px, and SIRT1 and FoxO1 protein expression in femoral tissues were significantly decreased in the OVX group of mice, whereas Tb.Sp, serum levels of ALP, TRACP5b, CTx-I, and MDA, as well as ROS levels and Ac-FoxO1 protein expression in femoral tissues were significantly higher (P < 0.05). Compared with the OVX group, BMD, Tb.Ar, Tb.N and Tb.Th, serum levels of BGP, SOD and GSH-Px, as well as SIRT1 and FoxO1 protein expression in femoral tissues were significantly elevated in both the E2 and AE groups, whereas Tb.Sp, serum levels of ALP, TRACP5b, CTx-I, and MDA, as well as ROS levels and Ac -FoxO1 protein expression in femoral tissues were significantly lower (P < 0.05). Compared with the AE group, BMD, Tb.Ar, Tb.N and Tb.Th, serum levels of BGP, SOD and GSH-Px, as well as SIRT1 and FoxO1 protein expression in femoral tissues were significantly lower in the AE+EX527 group, whereas Tb.Sp, serum levels of ALP, TRACP5b, CTx-I, and MDA, as well as ROS levels and Ac-FoxO1 protein expression in femoral tissues were significantly higher (P < 0.05). Conclusion: Aerobic exercise inhibited oxidative stress by activating the SIRT1/FoxO1 signaling pathway, thus improving bone loss in OVX mice. |
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