Khotib Junaidi, Pratiwi Asri Putri, Ardianto Chrismawan, Rahmadi Mahardian
Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University Jl Mulyorejo Campus C Unair, Surabaya 60115, Indonesia.
Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University Jl Mulyorejo Campus C Unair, Surabaya, Indonesia.
J Basic Clin Physiol Pharmacol. 2020 Jan 11;30(6):/j/jbcpp.2019.30.issue-6/jbcpp-2019-0332/jbcpp-2019-0332.xml. doi: 10.1515/jbcpp-2019-0332.
Background Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA. Methods The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection. Results MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01). Conclusions Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.
骨关节炎（OA）是最常见的关节疾病，也是关节疼痛、功能丧失和残疾的常见原因。这种疾病的严重程度总是与促炎细胞因子水平升高相关，促炎细胞因子在软骨损伤、滑膜炎和其他关节组织损伤中起重要作用。许多可溶性介质如细胞因子或前列腺素可增加软骨细胞产生基质金属蛋白酶的发现，引发了炎症状态的初步研究。多项研究表明，细胞因子如白细胞介素1β在这些关节发生的炎症发展中起主要作用。使用氨基葡萄糖作为美洛昔康治疗的辅助药物有望抑制炎性OA的发展。
通过单次关节内注射碘乙酸钠（MIA）诱导大鼠OA模型。观察OA的发展情况21天。此外，通过将低剂量美洛昔康1mg/kg体重与125、250或500mg/kg体重的氨基葡萄糖口服联合治疗28天，评估氨基葡萄糖作为美洛昔康治疗辅助药物降低IL-1β的效力。在第0、7、14、21、28、35、42和49天测量对痛觉过敏的反应和膝关节直径。在注射MIA后第21天和第49天测量IL-1β水平。
MIA注射成功诱导了OA，表现为热刺激潜伏期时间有显著差异（p<0.01），关节直径显著增加（p<0.01）。在第21天，MIA注射组的IL-1β水平显著降低（p=0.05）。美洛昔康和氨基葡萄糖的给药未导致膝关节直径显著减小（p>0.10），但能够显著增加热刺激潜伏期时间（p<0.01）。联合使用氨基葡萄糖和美洛昔康后，IL-1β水平也显著降低（p<0.01）。
综上所述，在美洛昔康治疗中使用氨基葡萄糖作为辅助药物，可能是由于美洛昔康通过系统性降低IL-1β来减轻OA发展的协同机制所致。
