N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models.
N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models.
复制标题
N-丁酰化透明质酸可改善动物模型中的痛风和高尿酸血症
DOI：
10.1080/13880209.2019.1672755
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发表时间：
2019-12
影响因子：
3.8
通讯作者：
Anastassiades T
中科院分区：
文献类型：
--
作者：
Li L;Wang D;Wang X;Bai R;Wang C;Gao Y;Anastassiades T
摘要背景：透明质酸(HA)在结构骨架、关节润滑、肾功能和细胞信号转导等方面发挥着重要作用。我们先前已经证明，部分N-丁酰化的低分子透明质酸(BHA)在培养的人巨噬细胞中显示出抗炎作用，炎症是由TL-4激动剂或低分子HA本身以剂量依赖的方式诱导的。目的：采用急性痛风性关节炎和高尿酸血症动物模型，观察BHA的抗炎、抗氧化和抗高尿酸血症作用。材料和方法：采用大鼠关节腔内注射尿酸单钠诱导的急性痛风性关节炎模型(n μ10/组)，以生理盐水对照组为对照，通过测定关节肿胀和血清炎症细胞因子水平来评价10和50 = g关节注射的抗炎作用。给高尿酸血症Balb/C小鼠腹腔注射奥特拉西钾和酵母膏，观察其抗氧化和抗高尿酸活性。结果：在痛风性关节炎大鼠模型中，高剂量(50 μg)牛血清白蛋白具有较强的抗炎作用，可使关节肿胀度和血清IL-1β、IL-8、γ、MCP-1水平分别降低5.56%、6.55%、15.58%和33.18%。在高尿酸血症小鼠模型中，低剂量的BHA(10 μg)能显著降低血清和肝脏的ROS水平14.87%和8.04%，提高肝脏超氧化物歧化酶水平12.77%，足以提供抗氧化活性。腹腔注射BHA可使高尿酸血症小鼠肝脏XO活性降低19.78%，血尿酸水平降低30.41%，从而抑制尿酸生成。结论：本研究首次证实BHA在体内具有抗炎、抗氧化和抗高尿酸血症的作用，提示BHA在痛风性关节炎和高尿酸血症的治疗中具有潜在的应用价值。
Abstract Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 μg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6–8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 μg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1β, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 μg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.
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影响因子：
4.9
作者：
Greenhill CJ;Jones GW;Nowell MA;Newton Z;Harvey AK;Moideen AN;Collins FL;Bloom AC;Coll RC;Robertson AA;Cooper MA;Rosas M;Taylor PR;O'Neill LA;Humphreys IR;Williams AS;Jones SA
通讯作者：
Jones SA
影响因子：
4.9
作者：
Harrold LR;Andrade SE;Briesacher BA;Raebel MA;Fouayzi H;Yood RA;Ockene IS
通讯作者：
Ockene IS
影响因子：
4.9
作者：
Busso N;So A
通讯作者：
So A
影响因子：
2.9
作者：
Davey, MW;Stals, E;Swennen, RL
通讯作者：
Swennen, RL
影响因子：
5
作者：
Keenan, Robert T.;Schlesinger, Naomi
通讯作者：
Schlesinger, Naomi