Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis
Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis
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DOI：
10.1155/2017/2515408
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发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Mookherjee, Neeloffer
中科院分区：
文献类型：
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作者：
Hemshekhar, Mahadevappa;Anaparti, Vidyanand;Mookherjee, Neeloffer
丁丙诺啡被推荐作为止痛剂用于动物模型，包括胶原性关节炎(CIA)的小鼠模型。然而，丁丙诺啡对疾病相关生物标记物表达的影响尚未很好地确定。我们研究了丁丙诺啡给药对CIA小鼠模型中疾病进展以及炎症和氧化应激标志物表达的影响。丁丙诺啡可改变CIA小鼠细胞因子、干扰素-γ、IL-6和基质金属蛋白酶-3的表达，以及氧化标记物如iNOS、超氧化物歧化酶(SOD1)和过氧化氢酶(CAT)的表达。由于丁丙诺啡是一种止痛剂，我们进一步监测了这些生物标记物的表达与早期类风湿性关节炎(RA)患者疼痛评分的相关性。在RA队列中，血清基质金属蛋白酶-3水平和抗氧化剂SOD1和CAT的血液mRNA表达与疼痛评分相关。我们已经证明，丁丙诺啡的给药改变了CIA小鼠模型中炎症和氧化应激相关分子标记物的表达。在使用丁丙诺啡作为止痛剂的动物实验中，这一警告需要考虑，因为它可能是用于预测治疗反应的小鼠研究中的一个混杂因素。此外，在人类队列中显示与疼痛评分相关的抗氧化酶可能在未来的研究中被探索为疼痛的生物标记物。
Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-gamma, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies.