[ZIF-8@Pt纳米酶用于清除活性氧治疗类风湿关节炎]。
[ZIF-8@Pt Nanozyme Used for Scavenging Reactive Oxygen Species in the Treatment of Rheumatoid Arthritis].
发表日期:2024 Jul 20
作者:
Xuelan Lei, Li Qiu, Fangxue DU
来源:
Arthritis & Rheumatology
摘要:
配制一种可清除活性氧(ROS)的铂金属缀合的ZIF-8纳米模拟酶(ZIF-8@Pt),并探索其在治疗类风湿性关节炎(RA)中的潜在应用。ZIF-8@ Pt纳米酶是通过原位还原产生的。然后对纳米酶进行表征并研究其模拟酶的能力。使用RAW264.7细胞进行细胞实验,将其分为三组,包括未处理组(UT)、接受脂多糖(LPS)的阳性对照组(指定为LPS组)和ZIF-8@Pt组。组接受 ZIF-8@Pt 和 LPS 治疗。进行细胞实验以评估 ZIF-8@Pt 通过清除细胞内 ROS 的抗炎特性。另一方面,在大鼠中诱导胶原诱导的关节炎(CIA)模型。与细胞实验中的分组类似,将大鼠分为三组,包括健康对照组(UT组)、膝关节局部注射PBS溶液的阳性对照组,称为对照组、膝关节局部注射ZIF-8@Pt溶液的治疗组,称为ZIF-8@Pt组。通过一般评价、影像学观察、炎症因子评估和病理学评估来评估ZIF-8@Pt对RA的治疗效果。体外实验显示细胞内ROS和LPS诱导的M1型水平存在显着差异。 LPS组和ZIF-8@Pt组之间的巨噬细胞极化(P<0.05)。体内实验显示,炎症因子包括白细胞介素-1β(IL-1β)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、精氨酸酶-1(Arg)水平存在显着差异。 -1) CIA大鼠膝关节LPS组和ZIF-8@Pt组之间的差异(P<0.05)。比较ZIF-8@Pt组和对照组的结果,病理学评估显示ZIF-8@Pt减少了局部缺氧,抑制了破骨细胞活性、新生血管形成和M1型巨噬细胞极化(P<0.05)。 8@Pt 酶模拟物通过 ROS 清除抑制巨噬细胞炎症极化,从而改善 RA 炎症。此外,ZIF-8@Pt纳米酶改善缺氧环境,抑制血管生成和骨质破坏,对RA具有良好的治疗效果。© 2024《四川大学学报(医学版)》编辑部版权所有Copyright ©2024 Journal of RA杂志编辑部四川大学(医学)。
To formulate a ZIF-8 nano mimetic enzyme conjugated with platinum metal (ZIF-8@Pt) that can scavenge reactive oxygen species (ROS) and to explore its potential applications in the treatment of rheumatoid arthritis (RA).The ZIF-8@Pt nanozyme was created by in situ reduction. Characterization of the nanozyme was then performed and its ability to mimic enzymes was investigated. Cell experiments were conducted using RAW264.7 cells, which were divided into three groups, including the untreated group (UT), the positive control group receiving lipopolysaccharide (LPS), which was designated as the LPS group, and the ZIF-8@Pt group receiving ZIF-8@Pt and LPS treatment. The cell experiments were conducted to evaluate the anti-inflammatory properties of ZIF-8@Pt through scavenging intracellular ROS. On the other hand, a collagen-induced arthritis (CIA) model was induced in rats. Similar to the group designations in the cell experiments, the rats were assigned to three groups, including a healthy control group (the UT group), a positive control group receiving a local injection of PBS solution in the knee joint, which was referred to as the control group, and a treatment group receiving a local injection of ZIF-8@Pt solution in the knee joint, which was referred to as the ZIF-8@Pt group. General evaluation, imaging observation, assessment of inflammatory factors, and pathological evaluation were performed to assess the therapeutic efficacy of ZIF-8@Pt against RA.The in vitro experiment revealed significant difference in the levels of intracellular ROS and LPS-induced M1-type macrophage polarization between the LPS group and the ZIF-8@Pt group (P<0.05). The in vivo experiment showed that significant difference in the levels of inflammatory factors, including interleukin-1β (IL-1β), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and arginase-1 (Arg-1) in the knee joints of the CIA rats between the LPS group and the ZIF-8@Pt group (P<0.05). Comparing the findings for the ZIF-8@Pt group and the control group, pathology assessment revealed that ZIF-8@Pt reduced local hypoxia and suppressed osteoclastic activity, neovascularization, and M1-type macrophage polarization (P<0.05).The ZIF-8@Pt enzyme mimetic inhibits macrophage inflammatory polarization by ROS scavenging, thereby improving inflammation in RA. Furthermore, the ZIF-8@Pt nanozyme improves the hypoxic environment and inhibits angiogenesis and bone destruction, demonstrating promising therapeutic efficacy for RA.© 2024《四川大学学报(医学版)》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).