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卡洛芬与鳄梨/大豆不皂化物、氨基葡萄糖和硫酸软骨素组合在软骨细胞微载体旋转培养中增强抗炎作用。

Anti-Inflammatory Effect of Carprofen Is Enhanced by Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination in Chondrocyte Microcarrier Spinner Culture.

机构信息

Department of Research and Development, Nutramax Laboratories, Inc., Edgewood, MD, USA.

College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

出版信息

Cartilage. 2020 Jan;11(1):108-116. doi: 10.1177/1947603518783495. Epub 2018 Jun 25.

Abstract

OBJECTIVE

Osteoarthritis is a painful, chronic joint disease affecting man and animals with no known curative therapies. Palliative nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but they cause adverse side effects prompting the search for safer alternatives. To address this need, we evaluated the anti-inflammatory activity of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) with or without the NSAID carprofen.

DESIGN

Canine chondrocytes were propagated in microcarrier spinner culture and incubated with (1) control medium, (2) ASU (8.3 µg/mL) + GLU (11 µg/mL) + CS (20 µg/mL) combination for 24 hours; and/or carprofen (40 ng/mL). Cultures were next incubated with control medium alone or IL-1β (10 ng/mL) for another 24 hours. Production of PGE, IL-6, IL-8, and MCP-1 (also known as CCL-2) were measured by ELISA.

RESULTS

Chondrocytes proliferated in microcarrier spinner culture and produced type II collagen and aggrecan. Stimulation with IL-1β induced significant increases in PGE, IL-6, IL-8, and MCP-1 production. The increases in production were suppressed by carprofen as well as [ASU+GLU+CS]. The combination of carprofen and [ASU+GLU+CS] reduced PGE production significantly more than either preparation alone. The inhibitory effect of carprofen on IL-6, IL-8, and MCP-1 production was significantly less than that of [ASU+GLU+CS], whereas the combination did not reduce the production of these molecules significantly more than [ASU+GLU+CS] alone.

CONCLUSIONS

The potentiating effect of [ASU+GLU+CS] on low-dose carprofen was identified in chondrocyte microcarrier spinner cultures. Our results suggest that the combination of low-dose NSAIDs like carprofen with [ASU+GLU+CS] could offer a safe, effective management for joint pain.

摘要

目的

骨关节炎是一种影响人和动物的疼痛性、慢性关节疾病,目前尚无已知的治愈疗法。常用的缓解疼痛的非甾体抗炎药(NSAIDs)有不良反应,因此需要寻找更安全的替代品。为满足这一需求,我们评估了鳄梨/大豆不皂化物(ASU)、氨基葡萄糖(GLU)和硫酸软骨素(CS)单独或与 NSAID 卡洛芬联合使用的抗炎活性。

设计

犬软骨细胞在微载体旋转培养器中传代培养,与(1)对照培养基、(2)ASU(8.3 µg/mL)+GLU(11 µg/mL)+CS(20 µg/mL)组合培养 24 小时;和/或卡洛芬(40 ng/mL)孵育。然后将培养物用对照培养基单独或 IL-1β(10 ng/mL)再孵育 24 小时。通过 ELISA 测量 PGE、IL-6、IL-8 和 MCP-1(也称为 CCL-2)的产生。

结果

软骨细胞在微载体旋转培养器中增殖,并产生 II 型胶原和聚集蛋白聚糖。IL-1β刺激显著增加 PGE、IL-6、IL-8 和 MCP-1 的产生。卡洛芬以及[ASU+GLU+CS]均抑制了产物的增加。卡洛芬和[ASU+GLU+CS]的组合降低 PGE 产物的效果明显优于单独使用任何一种制剂。卡洛芬抑制 IL-6、IL-8 和 MCP-1 产生的作用明显小于[ASU+GLU+CS],而联合用药并没有比单独使用[ASU+GLU+CS]更显著地降低这些分子的产生。

结论

在软骨细胞微载体旋转培养物中发现了[ASU+GLU+CS]对低剂量卡洛芬的增效作用。我们的结果表明,低剂量 NSAIDs 如卡洛芬与[ASU+GLU+CS]联合使用可能为关节疼痛提供安全有效的治疗方法。

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