摘要
Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.
目的研究柚皮素(NRG)对地塞米松(DEX)诱导的大鼠骨质疏松症(OP)的保护作用。方法使用AutoDock Vina 1.2.0软件对NRG进行分子对接。将48只雌性Wistar大鼠随机分为6组(每组8只):正常对照组(NC)、DEX组(7 mg/kg,肌肉注射)、低剂量NRG组(NRG-L;25 mg/kg,灌胃)、中剂量NRG组(NRG-M;50mg/kg,灌胃)、高剂量NRG组(NRG-H;100mg/kg,灌胃)和阿仑膦酸钠组(ALN;0.25mg/天,灌胃)。除NC组外,其他各组每周给予一次DEX诱导OP,持续5周。在初次DEX给药后的第3周开始,NRG-L、NRG-M、NRG-H和ALN组的大鼠连续3周每天接受相应的治疗,NC和DEX组未接受额外治疗。实验结束时收集血清样本,进行生化、骨更新、抗氧化、血脂谱和炎症细胞因子分析。对股骨进行物理参数测试和组织病理学检查。结果分子对接结果表明,NRG与降钙素(CT)、低密度脂蛋白(LDL)、骨形态形成性蛋白质(BMP)、血管内皮生长因子(VEGF)受体、叉头框转录因子和成骨前体细胞显示出良好的结合能量。给予25、50和100mg/kgNRG的大鼠血清生化指标出现显著改善,表现为耐酒石酸酸性磷酸酶(TRAP)降低,甲状旁腺激素(PTH)降低,以及骨钙素(OC)和CT水平升高(分别为P<0.05、P<0.01和P<0.001)。尽管股骨厚度、重量和长度无显著变化(P>0.05),但骨密度(BMD)显著增加(分别为P<0.01、P<0.001和P<0.001)。抗氧化酶标志物显著上调,谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平升高,同时丙二醛(MDA)水平降低(分别为P<0.05、P<0.01和P<0.001)。血脂水平也显著改善,胆固醇(CH)、甘油三酯(TG)和LDL水平降低,高密度脂蛋白(HDL)水平上升(分别为P<0.05、P<0.01和P<0.001)。炎症细胞因子水平降低,具体表现为肿瘤坏死因子(TNF)、白细胞介素(IL)-6和IL-1β降低(分别为P<0.05、P<0.01和P<0.001)。此外,组织学分析显示明显改善,与DEX组大鼠相比,经过NRG治疗的大鼠体重增加。结论研究结果提示NRG通过增加包括骨钙素和降钙素在内的骨转换标志物数量、恢复抗氧化状态、脂质代谢和炎症标志物,对DEX诱导的大鼠OP具有保护作用。
