沙利度胺在三硝基苯磺酸诱导的结肠炎中的治疗和预防作用：对肿瘤坏死因子-α、白细胞介素-12和血管内皮生长因子产生的协同效应
Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production.
作者信息
Carvalho Ana Teresa, Souza Heitor, Carneiro Antonio Jose, Castelo-Branco Morgana, Madi Kalil, Schanaider Alberto, Silv Flavia, Pereira Junior Fernando Antonio, Pereira Marcia G, Tortori Claudio, Dines Ilana, Carvalho Jane, Rocha Eduardo, Elia Celeste
机构信息
Departamento de Clinica Medica, Hospital Universitario Clementino Fraga Filho, Rua Barao da Torre, 666-101, Ipanema, Rio de Janeiro, RJ, Brazil.
出版信息
World J Gastroenterol. 2007 Apr 21;13(15):2166-73. doi: 10.3748/wjg.v13.i15.2166.
AIM
To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor alpha (TNF-alpha), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohnos disease (CD).
METHODS
Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-alpha and IL-12 were quantified in the supernatant of organ cultures by ELISA.
RESULTS
Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-alpha and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-alpha levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-alpha and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells.
CONCLUSION
Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-alpha, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.
目的
评估沙利度胺对2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎的治疗和预防作用。据报道，沙利度胺可下调肿瘤坏死因子α（TNF-α）、白细胞介素-12（IL-12）和血管内皮生长因子（VEGF）的表达，这些是克罗恩病（CD）肠道炎症的标志。
方法
将雄性Wistar大鼠分为五组，每组十只。四组接受TNBS乙醇溶液直肠灌注。第一组在诱导结肠炎后7天处死。第二组和第三组分别通过灌胃给予沙利度胺或安慰剂，并在14天处死。第四组在给予TNBS前6小时接受沙利度胺，并在诱导后7天处死。第五组作为对照组，未诱导结肠炎。进行结肠组织学炎症评分，并通过免疫组织化学检测固有层CD4 + T细胞、巨噬细胞和VEGF +细胞。通过酶联免疫吸附测定（ELISA）对器官培养上清液中的TNF-α和IL-12进行定量。
结果
与未用沙利度胺治疗的动物相比，用沙利度胺治疗的组炎症评分和VEGF +细胞百分比显著降低。与未接受沙利度胺的动物相比，用沙利度胺治疗的TNBS诱导的结肠炎动物中TNF-α和IL-12水平均显著降低。与未治疗的TNBS诱导的结肠炎动物相比，接受沙利度胺预防的动物中TNF-α水平也显著降低。肠道中TNF-α和IL-12水平与炎症评分和VEGF +细胞数量显著相关。
结论
沙利度胺通过抑制肠道中TNF-α、IL-（此处原文有误，应为IL-12）和VEGF的产生，显著减轻TNBS诱导的结肠炎。这一作用可能支持将沙利度胺作为CD特定患者的替代治疗方法。
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