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关节内注射双氯芬酸依托度酸透明质酸钠治疗大鼠膝骨关节炎的镇痛效果及关节炎改变。

Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model.

机构信息

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

出版信息

BMC Musculoskelet Disord. 2022 Nov 7;23(1):960. doi: 10.1186/s12891-022-05937-y.

DOI:10.1186/s12891-022-05937-y
PMID:36344944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9641934/
Abstract

BACKGROUND

Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA).

METHODS

We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord.

RESULTS

Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration.

CONCLUSION

DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.

摘要

背景

双氯芬酸透明质酸钠（DF-HA）是一种最近开发的双氯芬酸和透明质酸的镇痛结合物，对急性关节炎具有镇痛和抗炎作用。在这项研究中，我们使用碘乙酸单酯（MIA）大鼠模型研究了其对骨关节炎的镇痛作用。

方法

我们将 MIA 注射到 8 只 6 周龄雄性 Sprague-Dawley 大鼠的右膝关节中。4 周后，将大鼠随机注射 DF-HA 或载体到右膝关节。在 MIA 注射后 7 周，所有大鼠的右膝关节中均注射荧光金（FG）和无菌生理盐水。我们每周通过 von Frey 测试评估痛觉过敏，共 8 周。每隔 2 周对右膝关节进行计算机断层扫描（CT）作为影像学评估。所有大鼠在 MIA 给药后 8 周处死，用于右膝关节的组织学评估和 DRG 和脊髓的免疫组织化学评估。我们还评估了背根神经节（DRG）中 FG 标记的降钙素基因相关肽（CGRP）-免疫反应性（ir）神经元和脊髓中离子钙结合衔接分子 1（Iba1）-ir 小胶质细胞的数量。

结果

DF-HA 给药显著改善了疼痛敏感性，并分别降低了 DRG 和脊髓中的 CGRP 和 Iba1 表达。然而，尽管给予了 DF-HA，右膝关节的 CT 和组织学评估仍显示出相似水平的关节畸形。

结论

DF-HA 对骨关节炎疼痛具有镇痛作用，但不影响关节畸形。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/b09f5f0cc0bb/12891_2022_5937_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/db2022330fa1/12891_2022_5937_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/6dfa12fa1efa/12891_2022_5937_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/5f45937fd119/12891_2022_5937_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/b09f5f0cc0bb/12891_2022_5937_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/db2022330fa1/12891_2022_5937_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/1c48d02800ea/12891_2022_5937_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/6b5f9f567190/12891_2022_5937_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/6dfa12fa1efa/12891_2022_5937_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/5f45937fd119/12891_2022_5937_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1abe/9641934/b09f5f0cc0bb/12891_2022_5937_Fig6_HTML.jpg

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