Bersani-Amado Luiz Eduardo, Dantas Jaílson Araujo, Damião Marcio José, Rocha Bruno Ambrósio, Besson Jean Carlos Fernando, Bastos Rafael Lucena, Silva Letícia Nicoletti, Bersani-Amado Ciomar Aparecida, Cuman Roberto Kenji Nakamura
Department of Medicine-Uningá Faculty, Avenida Morangueira, PR 317, 6114, Maringá, Paraná, Brazil.
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Fundam Clin Pharmacol. 2016 Feb;30(1):35-46. doi: 10.1111/fcp.12162. Epub 2015 Nov 18.
This study investigated the kinetics of cytokines that are involved in the development of interstitial fibrosis in mice that were subjected to UUO, the interstitial type I and III collagen deposition, and the effects of Thalido and Dexa treatment on these parameters. Inbred C57BL/6 mice were divided into the groups: Normal (not submitted surgery), Sham (sham surgery), Control (UUO treated with 0.5% carboxymethyl cellulose), Thalido (UUO treated with 5 mg/kg thalidomide), and Dexa (UUO treated with 1 mg/kg dexamethasone). The treatments began the day before surgery and were administered once daily by gavage for 1, 7, or 14 days. At the end of each treatment period, blood samples were collected for the determination of creatinine, urea, cytokines. The Control group exhibited a increase in creatinine concentration compared with the Normal and Sham groups within the first 24 h after UUO, which remained high until days 7 and 14. The urea concentration was higher on days 7 and 14 in the Control group compared with the Sham group. In the Thalido and Dexa groups, a reduction of serum creatinine concentration was seen on day 14. Treatment with Dexa reduced the serum concentration of urea on day 7. The serum concentrations of cytokines (TNF-α, IL-1β, IL-6, IL-10 and IL-17) and chemokines (KC, MIG, bFGF) increased in UUO mice at all of the sampling times. The Dexa and Thalido groups exhibited alterations in the concentrations of these cytokines, suggesting the involvement of anti-inflammatory and immunomodulatory mechanisms that may have modified the fibrosis framework.
本研究调查了参与单侧输尿管梗阻(UUO)小鼠间质纤维化发展过程的细胞因子动力学、间质I型和III型胶原沉积,以及沙利度胺和地塞米松治疗对这些参数的影响。近交系C57BL/6小鼠被分为以下几组:正常组(未接受手术)、假手术组(假手术)、对照组(用0.5%羧甲基纤维素处理的UUO组)、沙利度胺组(用5mg/kg沙利度胺处理的UUO组)和地塞米松组(用1mg/kg地塞米松处理的UUO组)。治疗在手术前一天开始,通过灌胃每日给药一次,持续1、7或14天。在每个治疗期结束时,采集血样以测定肌酐、尿素和细胞因子。与正常组和假手术组相比,对照组在UUO后的前24小时内肌酐浓度升高,直至第7天和第14天仍保持在高位。与假手术组相比,对照组在第7天和第14天尿素浓度更高。在沙利度胺组和地塞米松组中,第14天时血清肌酐浓度降低。地塞米松治疗在第7天时降低了血清尿素浓度。在所有采样时间点,UUO小鼠的细胞因子(TNF-α、IL-1β、IL-6、IL-10和IL-17)和趋化因子(KC、MIG、bFGF)血清浓度均升高。地塞米松组和沙利度胺组这些细胞因子的浓度出现了变化,提示抗炎和免疫调节机制的参与,这可能改变了纤维化结构。