摘要
目的观察膝关节腔内注射负载软骨衍生形态发生蛋白1(CDMP-1)和地塞米松(DEX)的盘状脂质纳米粒(DLNPs)对膝关节炎新西兰兔血清和滑膜组织中炎性因子的影响,并探讨其治疗关节炎的作用机制。方法健康新西兰兔35只,随机分为5组:对照组、模型组、DEX组、CDMP-1组、DLNPs组,每组7只,其中模型组、DEX组、CDMP-1组、DLNPs组新西兰兔采用Hulth改良法制备膝关节炎新西兰兔模型。造模成功后,分别在第1、4、7、10天于膝关节腔内注射药物,DEX组注射9.8%的DEX,CDMP-1组注射CDMP-1,DLNPs组注射负载CDMP-1和DEX的纳米颗粒DLNPs,对照组、模型组不给药。造模成功后第13天处死,取腹主动脉血,采用ELISA法检测血清中炎性因子白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、前列腺素2(PGE2);取膝关节滑膜组织,采用BCA法检测滑膜组织中炎性因子IL-1β、TNF-α、基质金属蛋白酶-13(MMP13)。结果模型组、DEX组、CDMP-1组、DLNPs组新西兰兔血清中IL-1β、IL-6、TNF-α、PGE2水平和滑膜组织中IL-1β、TNF-α、MMP-13相对表达量与对照组相比均显著升高(P均<0.05),DEX组、CDMP-1组、DLNPs组新西兰兔血清中IL-1β、IL-6、TNF-α、PGE2水平和滑膜组织中IL-1β、TNF-α、MMP-13相对表达量与模型组相比均显著降低(P均<0.05),DEX组、CDMP-1组、DLNPs组新西兰兔血清中IL-1β、IL-6、TNF-α、PGE2水平和滑膜组织中IL-1β、TNF-α、MMP-13相对表达量组间相比,P均<0.05,且CDMP-1组最高、DLNPs组最低(P均<0.05)。结论与单独注射DEX或CDMP-1相比,膝关节腔内注射负载CD‐MP-1和DEX的盘状脂质纳米粒DLNPs可以显著降低膝关节炎新西兰兔血清和滑膜组织中炎性因子的水平。
objective To observe the effects of intra-articular injection of discoid lipid nanoparticles(DLNPs)loaded with cartilage-derived morphogenetic protein 1(CDMP-1)and dexamethasone(DEX)on inflammatory factors in serum and synovial tissues of New Zealand rabbits with knee arthritis(OA),and to explore its mechanism in the treatment of OA.Methods Thirty-five healthy New Zealand rabbits were randomly divided into five groups:the control group,model group,DEX group,CDMP-1 group,and DLNPs group,with 7 rabbits in each group.Except for the control group,knee OA models in the other groups were established with the Hulth method,then,drugs were injected into the knee joint cavity on the 1,4,7,and 10 days.The rabbits in the DEX group were injected with 9.8%DEX,the CDMP-1 group with CDMP-1,and the DLNPs group with DLNPs,but the rabbits in the control group and model group were not administered.The rabbits were sacrificed on the 13th day after the successful modeling,and abdominal aortic blood was taken,and the serum inflammatory factors,interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and prostaglandin 2(PGE2)were detected by ELISA;in the synovial tissues of the knee joint,the inflammatory factors IL-1β,TNF-α,and matrix metalloproteinase-13(MMP13)were detected by the BCA method.Results Compared with the control group,the serum levels of IL-1β,IL-6,TNF-α,and PGE2 and the relative expression levels of IL-1β,TNF-α,and MMP-13 in the synovial tissues increased in the model group,DEX group,CDMP-1 group,and DLNPs group(all P<0.05).Compared with the model group,the serum levels of IL-1β,IL-6,TNF-α,and PGE2 and the relative expression levels of IL-1β,TNF-α,and MMP-13 in the synovial tissues decreased in the DEX group,CDMP-1 group,and DLNPs group(all P<0.05).Significant differences were found in the serum levels of IL-1β,IL-6,TNF-α,PGE2 and the relative expression levels of IL-1β,TNF-α,and MMP-13 in the synovial tissue among the DEX group,CDMP-1 group,and DLNPs group(all P<0.05),with the highest in the CDMP-1 group and the lowest in the DLNPs group(all P<0.05).Conclusion Compared with the injection of DEX or CDMP-1 alone,intra-articular injection of CDMP-1 and DEX-loaded nanoparticle DLNPs in the knee joint cavity can significantly reduce the levels of inflammatory factors in the serum and synovial tissues of New Zealand rabbits with knee arthritis.
作者
吴晓东
李朋朋
程建
霍维玲
李国栋
WU Xiaodong;LI Pengpeng;CHENG Jian;HUO Weiling;LI Guodong(Department of Orthopedics,Xuzhou Central Hospital,Xuzhou 221009,China;不详)
出处
《山东医药》
CAS
2021年第33期44-47,共4页
Shandong Medical Journal
基金
徐州市科学与技术局项目(KC18039)
江苏省博士后资助项目(2018K244C)
徐州市临床技术骨干研究项目(2018GG027)。
