Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Faslpr mice by N-3 fatty acids
Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Faslpr mice by N-3 fatty acids
复制标题
DOI：
10.1080/07315724.2005.10719466
复制
发表时间：
2005-06-01
影响因子：
3.5
通讯作者：
Fernandes, G
中科院分区：
文献类型：
--
作者：
Bhattacharya, A;Rahman, M;Fernandes, G
目的：类风湿关节炎（RA）是一种系统性自身免疫性炎症性疾病，涉及软骨和关节旁骨的破坏，通常伴有骨密度（BMD）降低和骨折风险增加。抗炎ω -3脂肪酸可以预防MRL/pr小鼠关节炎模型和人类的关节炎和骨质流失。方法：本研究采用双能x线吸收仪（DEXA）测量6周龄开始长期饲喂10% n-3（鱼油）和n-6（玉米油）脂肪酸对RA雌性MRL/lpr模型小鼠不同骨区骨密度（BMD）的影响。12月龄处死小鼠后，测定脾脏抗氧化酶活性，采用RT-PCR法测定淋巴结nf - κ B配体受体激活物（RANKL）和骨保护素（OPG） mRNA表达量，并测定腿关节滑膜炎情况。结果：在6、9、12月龄时，FO喂养小鼠股骨远端、胫骨近端和腰椎的骨密度显著高于CO喂养小鼠（p < 0.05）。鱼油组小鼠脾脏过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性显著高于一氧化碳组（p < 0.01）。膝关节组织学显示，CO喂养的小鼠有轻度滑膜炎，而FO喂养的小鼠没有。RT-PCR分析显示，与CO饲喂小鼠相比，FO饲喂小鼠淋巴结RANKL mRNA表达降低（p < 0.001）， OPG mRNA表达增强（p < 0.01）。结论：这些结果表明，长期饲喂鱼油对维持该小鼠模型较高的骨密度和较低的滑膜炎有有益作用。这些有益的影响可能部分是由于在食用FO的小鼠中，抗氧化酶活性增加，RANKL表达减少，OPG表达增加，从而改变了RANKL/OPG比率。这些对骨密度的显著有益作用表明，鱼油可作为一种有效的膳食补充剂，预防RA患者骨密度损失。
Objective: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/pr mice model of arthritis and in humans.Methods: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints.Results: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice.Conclusions: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.