探討玻尿酸－四環黴素膠體經由關節內注射具協同性治療退化性關節炎

THE COMBINED EFFECT OF HYALURONIC ACID AND DOXYCYCLINE VIA INTRA-ARTICULAR INJECTABLE GELS FOR THE TREATMENT OF OSTEOARTHRITIS

藍絜(Jai Lan)

指導教授 ： 陳建和

共同指導教授 ： 許明照 ； 梁有志(Yu-Chih Liang)

臺北醫學大學/醫學院/醫學科學研究所/碩士(2008年)

https://doi.org/10.6831/TMU.2008.00017

摘要

退化性關節炎是一種緩慢漸進式的退化性疾病，目前治療關節炎藥物的研究重點，在於進一步修飾已知傳統藥物之官能基，使其成為具有改善連結組織結構(CTSMAs)以及減緩關節炎症狀之藥物(DMODs)。國外臨床上四環黴素(DC)已普遍使用於治療關節炎，它能抑制第一型介白素B(IL-1B) 和基質金屬蛋白酶類(MMPs)的生合成，也能改善subchondrobone的組織結構，長期使用能有效的治療關節炎。關節腔直接注射玻尿酸(HA)亦是目前臨床上廣泛用於治療關節炎的方式，可抑制MMPs的表現及促進醣胺聚醣(GAG)生成外，亦具備高黏度與黏彈的特性，給予關節物理性的保護並提供止痛的效果。本篇論文是利用鋅離子連結DC及玻尿酸，於外科手術引發關節炎之紐西蘭白兔做關節腔直接注射法來驗證HA-DC膠體是否具備協同之治療效果。本次研究結果顯示，此HA-DC膠體能提供較佳之黏彈性質，並具有止痛功能；此巨型網狀結構使得HA不易被降解，可延緩並增強藥物保護關節軟骨之效果。而關節軟骨染色與切片的結果更顯示，使用HA-DC膠體之組別具有較正常之關節軟骨分佈，只產生少量的磨損裂縫及骨刺，顯示此藥物產生修復與抑制軟骨降解之效果；且相較於單獨使用HA或DC顯示了更佳的治療效果。這些實驗結果符合我們先前一系列的細胞實驗與膠體備製測試，數據皆顯示此HA-DC膠體結構確實能有效減緩關節炎症狀並提供良好之止痛效果。

關鍵字

關節炎(OA) ； 減緩關節炎症狀藥物(Disease-modifying osteoarthritis drugs，DMODs) ； 改善連接組織結構藥物 (connective tissue structure- modifying agents，CTSMAs) ； 四環黴素(Doxycycline, DC) ； 基質金屬蛋白?類(MMPS) ； 第二型膠原蛋白(type II collagen) ； 玻尿酸Hyaluronic acid (HA)

並列摘要

Osteoarthritis (OA) is a degenerative disease that disunites the extra cellular matrix (ECM) of articular cartilage and is arduous to cure because cartilage is a complex and nonvascular tissue. Treatment of OA has targeted modifiable reagent to be the connective tissue structure-modifying agents (CTSMAs) and disease- modifying osteoarthritis drugs (DMODs), such as hyaluronic acid (HA) or modified tetracycline. However, the aim of this present study was to examine whether intra-articular injection of the HA-DC gel restores the matrix of arthritic knee joints in rabbit model. The injectable HA-DC gel was composed of HA, doxycycline (DC) and zinc chloride. It was administered five times (at days 0, 3, 6, 9 and 12) into the partial meniscectomy and unilateral fibular ligament transected knee joints of 13-week old New Zealand White rabbits, and the effects of HA-DC gel injection were compared with that of DC, HA or normal saline. Evaluation of OA progression was histopathologically by Alcian blue and eosin staining, by the modified grading method and by scanning electron microscopy at day 14. HA-DC gel group showed smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation than the other groups. Normal distribution of chondrocytes or inflammation was noticed in areas of slight OA changes in the HA-DC gel group indicating regenerative ability. HA-DC gel seemed to inhibit the progression of osteoarthritis by protecting the layers of articular cartilage, decreasing the degree of pain and restoring the elasticviscosity. Both macroscopic and histological data of this study supported those biochemical results and gel preparation of previous studies showing the synergistic therapeutic effect of HA-DC gel on osteoarthritis.

並列關鍵字

osteoarthritis (OA) ； disease-modifying osteoarthritis drugs (DMODs) ； connective tissue structure- modifying agents (CTSMAs) ； Doxycycline (DC) ； type II collagen ； matrix metalloproteinases (MMPs) ； Hyaluronic acid (HA)

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