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一种来自绿藻粗枝软骨藻的凝集素可减轻酵母聚糖诱导的关节炎大鼠颞下颌关节的机械性痛觉过敏和炎症。

A lectin from the green seaweed Caulerpa cupressoides reduces mechanical hyper-nociception and inflammation in the rat temporomandibular joint during zymosan-induced arthritis.

作者信息

da Conceição Rivanor Renata Line, Chaves Hellíada Vasconcelos, do Val Danielle Rocha, de Freitas Alice Ramos, Lemos Jonas Cavalcante, Rodrigues José Ariévilo Gurgel, Pereira Karuza Maria Alves, de Araújo Ianna Wivianne Fernandes, Bezerra Mirna Marques, Benevides Norma Maria Barros

机构信息

Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Faculty of Dentistry, Federal University of Ceará, Sobral, Ceará, Brazil.

出版信息

Int Immunopharmacol. 2014 Jul;21(1):34-43. doi: 10.1016/j.intimp.2014.04.009. Epub 2014 Apr 24.

Abstract

Seaweed lectins have been widely investigated as anti-nociceptive and anti-inflammatory agents. This study analyzed the anti-nociceptive and anti-inflammatory responses of a lectin from the green seaweed Caulerpa cupressoides (CcL) on zymosan-induced arthritis of the rat temporomandibular joint (TMJ). Rats received i.v. CcL 30 min prior to injection of zymosan (2mg/art.) or 0.9% saline into the left TMJ. Mechanical hyper-nociception was measured by the electronic von Frey method at baseline and 4h after zymosan injection. Animals were euthanized 6h after zymosan injection and the synovial fluid was collected for leukocyte counting and myeloperoxidase activity assessment. Other animals were treated with ZnPP-IX (3mg/kg; s.c.), a specific heme oxygenase-1 pathway inhibitor, and naloxone (10 μg/art.), a nonselective opioid receptor antagonist. TMJ tissues were excised to perform histopathological and immunohistochemistry analyses. CcL (0.1, 1 or 10mg/kg) significantly reduced zymosan-induced hyper-nociception (81, 83 and 89.5%, respectively) and inhibited the leukocyte influx (77.3, 80.7 and 98.5%, respectively) compared with the zymosan-only group, as confirmed by myeloperoxidase activity; however, treatment with naloxone or ZnPP-IX did not revert the effects of CcL (10mg/kg), suggesting that the naloxone-sensitive opioid and heme oxygenase-1 pathways are not involved. CcL also reduced the leukocyte influx and the expression of IL-1β and TNF-α in the TMJ, based on histopathological and immunohistochemistry analyses, respectively. Therefore, CcL reduces TMJ hyper-nociception and inflammation with a mechanism that is partially dependent on TNF-α and IL-1β inhibition. CcL reveals a potentially valuable alternative tool for future studies of TMJ disorders.

摘要

海藻凝集素作为抗伤害性和抗炎剂已得到广泛研究。本研究分析了来自绿藻粗枝软骨藻(CcL)的一种凝集素对大鼠颞下颌关节(TMJ)酵母聚糖诱导的关节炎的抗伤害性和抗炎反应。大鼠在向左侧TMJ注射酵母聚糖(2mg/只)或0.9%生理盐水前30分钟静脉注射CcL。在基线和酵母聚糖注射后4小时,通过电子von Frey法测量机械性痛觉过敏。酵母聚糖注射后6小时对动物实施安乐死,并收集滑液用于白细胞计数和髓过氧化物酶活性评估。其他动物用锌原卟啉-IX(3mg/kg;皮下注射)(一种特异性血红素加氧酶-1途径抑制剂)和纳洛酮(10μg/只)(一种非选择性阿片受体拮抗剂)进行治疗。切除TMJ组织以进行组织病理学和免疫组织化学分析。与仅注射酵母聚糖的组相比,CcL(0.1、1或10mg/kg)显著降低了酵母聚糖诱导的痛觉过敏(分别为81%、83%和89.5%),并抑制了白细胞流入(分别为77.3%、80.7%和98.5%),髓过氧化物酶活性证实了这一点;然而,用纳洛酮或锌原卟啉-IX治疗并未逆转CcL(10mg/kg)的作用,表明纳洛酮敏感的阿片和血红素加氧酶-1途径未参与其中。基于组织病理学和免疫组织化学分析,CcL还分别减少了TMJ中的白细胞流入以及IL-1β和TNF-α的表达。因此,CcL通过部分依赖于TNF-α和IL-1β抑制的机制降低TMJ痛觉过敏和炎症。CcL为未来颞下颌关节疾病的研究揭示了一种潜在有价值的替代工具。

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