Guerra Gerlane Coelho Bernardo, de Menezes Marília Stefani Souza, de Araújo Aurigena Antunes, de Araújo Júnior Raimundo Fernandes, de Medeiros Caroline Addison Carvalho Xavier
Post Graduation Program in Biological Sciences/Federal University of Rio Grande do Norte, Department Biophysical and Pharmacology, Federal University of Rio Grande do Norte.
Biol Pharm Bull. 2016;39(11):1793-1801. doi: 10.1248/bpb.b16-00296.
The objective of this study was to study the effect of olmesartan medoxomil (OLM), an antihypertensive drug, on intra-articular inflammation induced by zymosan (Zy) in Wistar rats. Intra-articular inflammation was induced in the right knees of rats by 1 mg Zy dissolved in saline. The animals were divided into the following groups: saline only (oral saline and intra-articular saline); Zy only (intra-articular Zy and oral saline), and intra-articular Zy and oral OLM (5, 15, or 30 mg/kg) or diclofenac sodium (SD; 100 mg/kg). Twenty-four hours after Zy injection, synovial fluid was collected for total leukocyte counts, blood was collected for biochemical measurements, and synovial tissue was collected for histopathology, immunohistochemistry, immunofluorescence and myeloperoxidase (MPO), malonaldehyde (MDA), and non-protein sulphydryl (NPSH) assays. OLM doses of 15 and 30 mg/kg had protective effects, as evidenced by improved histopathological parameters of synovium, reduced total leukocyte counts, reduced MPO and MDA levels, and increased NPSH group levels compared with the Zy group. OLM reduced immunostaining for cyclooxygenase 2, tumour necrosis factor and interleukin 17 and increased immunostaining for superoxide dismutase and glutathione peroxidase. SD produced similar results. The drugs studied caused no change in biochemical parameters of the animals. OLM showed protective effects in this model of Zy-induced intra-articular inflammation.
本研究的目的是探讨抗高血压药物奥美沙坦酯(OLM)对Wistar大鼠中由酵母聚糖(Zy)诱导的关节内炎症的影响。将1mg溶解于盐水中的Zy注射到大鼠右膝以诱导关节内炎症。动物被分为以下几组:仅生理盐水组(口服生理盐水和关节内注射生理盐水);仅Zy组(关节内注射Zy和口服生理盐水),以及关节内注射Zy并口服OLM(5、15或30mg/kg)或双氯芬酸钠(SD;100mg/kg)组。在注射Zy后24小时,收集滑液进行白细胞总数计数,收集血液进行生化测量,并收集滑膜组织进行组织病理学、免疫组织化学、免疫荧光以及髓过氧化物酶(MPO)、丙二醛(MDA)和非蛋白巯基(NPSH)测定。与Zy组相比,15和30mg/kg剂量的OLM具有保护作用,表现为滑膜组织病理学参数改善、白细胞总数减少、MPO和MDA水平降低以及NPSH组水平升高。OLM减少了环氧合酶2、肿瘤坏死因子和白细胞介素17的免疫染色,并增加了超氧化物歧化酶和谷胱甘肽过氧化物酶的免疫染色。SD产生了类似的结果。所研究的药物对动物的生化参数没有影响。在这种Zy诱导的关节内炎症模型中,OLM显示出保护作用。