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木犀草素通过抑制蛋鸡破骨细胞生成对镉抑制的骨骼生长的影响。

Effect of Luteolin on cadmium-inhibited bone growth via suppressing osteoclastogenesis in laying chickens.

作者信息

Tong Xishuai, Fu Xiaohui, Gong Anqing, Yu Gengsheng, Chen Naineng, Chen Bing, Gu Jianhong, Liu Zongping

机构信息

Joint International Research Laboratory of Agriculture and Agri-Product Safety of The Ministry of Education of China, Institute of Agricultural Science and Technology Development, College of Veterinary Medicine, Yangzhou University, Yangzhou, P. R. China.

Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, P. R. China.

出版信息

J Anim Sci. 2025 Jan 4;103. doi: 10.1093/jas/skaf033.

DOI:10.1093/jas/skaf033
PMID:39921628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11912829/
Abstract

Luteolin (Lut) is a flavonoid derived from several plant sources. Cadmium (Cd) is a widespread environmental contaminant and potential toxin with detrimental effects on animal health. However, the effect of Lut on Cd-induced inhibition of bone growth in laying chickens remains unclear. This study investigates the effects of Lut on Cd-induced inhibition of bone growth in the femur and tibia of laying chickens. A total of sixty 1-d-old green-eggshell yellow feather laying chickens were randomly assigned to 4 groups after a 5-d acclimation period: basal diet (Con), cadmium chloride (CdCl2, Cd), Lut, and Lut + Cd. Bone microstructure, serum biomarkers of bone remodeling, the levels of Cd, calcium (Ca), phosphorus (P), and trace metal elements were assessed using the micro-computed tomography (Micro-CT), enzyme-linked immunosorbent assay (ELISA), and microwave digestion, respectively. Bone remodeling biomarkers, late endosomal/lysosomal adaptor and MAPK and mTOR activator 1 (LAMTOR1), as well as the phosphorylation of AMP-activated protein kinase α (AMPKα) and protein kinase B (Akt), were quantified using the qRT-PCR and western blot. The results indicated that Lut effectively mitigated Cd-induced bone mass loss compared to the Cd group, resulting in increased bone volume (BV), bone surface/BV (BS/BV), connectivity density (Conn.Dn), and the length and weight of the femur and tibia in laying chickens. Mechanistically, compared to the Cd group, Lut restored the ratio of osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) in serum and bone tissue, enhanced the expression of bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and Osterix (OSX), while reducing the levels of Ca, Cd, and alkaline phosphatase (ALP) activity, as well as the expression of osteopontin (OPN), c-Fos, osteoclast stimulatory-transmembrane protein (OC-STAMP), tartrate-resistant acid phosphatase, cathepsin K (CTSK), matrix metalloprotein-9 (MMP-9), LAMTOR1, and the phosphorylation of AMPKα and Akt. Therefore, Lut alleviates Cd-induced damage to the femur and tibia of chickens by promoting osteogenesis and inhibiting osteoclastogenesis, positioning Lut as a potential therapeutic plant extract for enhancing bone growth in laying chickens.

摘要

木犀草素(Lut)是一种源自多种植物的黄酮类化合物。镉(Cd)是一种广泛存在的环境污染物和潜在毒素,对动物健康具有有害影响。然而,Lut对镉诱导的蛋鸡骨骼生长抑制的影响尚不清楚。本研究调查了Lut对镉诱导的蛋鸡股骨和胫骨骨骼生长抑制的影响。在5天的适应期后,将总共60只1日龄的绿壳黄羽蛋鸡随机分为4组:基础日粮组(Con)、氯化镉组(CdCl2,Cd)、Lut组和Lut + Cd组。分别使用显微计算机断层扫描(Micro-CT)、酶联免疫吸附测定(ELISA)和微波消解技术评估骨微结构、骨重塑的血清生物标志物、镉、钙(Ca)、磷(P)和微量元素的水平。使用qRT-PCR和蛋白质印迹法对骨重塑生物标志物、晚期内体/溶酶体衔接蛋白以及MAPK和mTOR激活剂1(LAMTOR1),以及AMP激活的蛋白激酶α(AMPKα)和蛋白激酶B(Akt)的磷酸化进行定量分析。结果表明,与镉组相比,Lut有效减轻了镉诱导的骨量损失,导致蛋鸡的骨体积(BV)、骨表面/BV(BS/BV)、连通性密度(Conn.Dn)以及股骨和胫骨的长度和重量增加。从机制上讲,与镉组相比,Lut恢复了血清和骨组织中骨保护素(OPG)/核因子κB受体激活剂配体(RANKL)的比例,增强了骨形态发生蛋白2(BMP-2)、 runt相关转录因子2(Runx2)、骨钙素(OCN)和osterix(OSX)的表达,同时降低了Ca、Cd和碱性磷酸酶(ALP)活性水平,以及骨桥蛋白(OPN)、c-Fos、破骨细胞刺激跨膜蛋白(OC-STAMP)、抗酒石酸酸性磷酸酶、组织蛋白酶K(CTSK)、基质金属蛋白酶9(MMP-9)、LAMTOR1的表达以及AMPKα和Akt的磷酸化。因此,Lut通过促进成骨作用和抑制破骨细胞生成来减轻镉对鸡股骨和胫骨的损伤,使Lut成为一种潜在的用于促进蛋鸡骨骼生长的治疗性植物提取物。

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本文引用的文献

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Oligomeric proanthocyanidins ameliorates osteoclastogenesis through reducing OPG/RANKL ratio in chicken's embryos.低聚原花青素通过降低鸡胚中 OPG/RANKL 比值来改善破骨细胞生成。
Poult Sci. 2024 Jun;103(6):103706. doi: 10.1016/j.psj.2024.103706. Epub 2024 Mar 30.
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Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol.芦丁和活性炭对黄曲霉毒素暴露肉鸡生长性能、免疫功能和抗氧化能力的改善作用。
Toxins (Basel). 2023 Jul 26;15(8):478. doi: 10.3390/toxins15080478.
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Vitamin D Alleviates Cadmium-Induced Inhibition of Chicken Bone Marrow Stromal Cells' Osteogenic Differentiation In Vitro.维生素D减轻镉诱导的鸡骨髓间充质干细胞体外成骨分化抑制
Animals (Basel). 2023 Aug 7;13(15):2544. doi: 10.3390/ani13152544.
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Potential effect of luteolin, epiafzelechin, and albigenin on rats under cadmium-induced inflammatory insult: and approach.木犀草素、表阿夫儿茶精和白花青素对镉诱导的炎症损伤大鼠的潜在影响:一种体外和体内方法。
Front Chem. 2023 Mar 1;11:1036478. doi: 10.3389/fchem.2023.1036478. eCollection 2023.
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Immunopharmacological Activities of Luteolin in Chronic Diseases.木樨草素在慢性疾病中的免疫药理学活性。
Int J Mol Sci. 2023 Jan 21;24(3):2136. doi: 10.3390/ijms24032136.
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Bone morphogenetic protein 4 is involved in cadmium-associated bone damage.骨形态发生蛋白 4 参与镉相关的骨骼损伤。
Toxicol Sci. 2023 Feb 17;191(2):201-211. doi: 10.1093/toxsci/kfac121.
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The origins and roles of osteoclasts in bone development, homeostasis and repair.破骨细胞在骨骼发育、稳态和修复中的起源和作用。
Development. 2022 Apr 15;149(8). doi: 10.1242/dev.199908. Epub 2022 May 3.
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Front Endocrinol (Lausanne). 2022 Mar 8;13:866641. doi: 10.3389/fendo.2022.866641. eCollection 2022.
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