己酮可可碱对内毒素诱导的核因子kappaB及其炎性因子的影响

Pentoxifylline inhibits endotoxin-induced NF-kappa B activation and proinflammatory cytokines production in vivo

目的 观察内毒素腹腔感染大鼠肠道炎性细胞因子及其核因子kappaB(NF kappaB) 的变化,探讨不同剂量己酮可可碱(PTX)的干预作用。方法 腹腔注射内毒素(LPS)5mg/kg建立 脓毒症模型。成年雄性Wistar大鼠被随机分为对照组,LPS组(5mg/kg腹腔注射),LPS+PTX组 (LPS5mg/kg腹腔注射,PTX6.25、12.5、25、50、100mg/kg静脉注射),PTX组(PTX100mg/kg 静脉注射)。2h后放血处死动物,取肠道组织保存于液氮中备用。凝胶电迁移(EMSA)测定肠道的 NF kappaB活性,酶联免疫吸附(ELISA)测定肠道肿瘤坏死因子α(TNF α)及白细胞介素 6(IL 6)、 白细胞介素 10(IL 10)的水平。结果 腹腔注射LPS可以增强肠道组织的NF kappaB活性,升高 组织TNF α、IL 6、IL 10水平,各剂量PTX都可以抑制肠道的NF kappaB活性,抑制TNF α、IL 6 的水平,但增强IL 10的释放,并与剂量相关。结论 PTX可以抑制LPS在体内的激活,其作用机制 可能与对NF kappaB的抑制有关。

Objective To investigate the effects of different doses of pentoxifylline(PTX) on the endotoxin-induced inflammatory cytokine production and nuclear factor kappa B (NF-kappa B)activation in vivo. Methods Sepsis was induced in rats via injection of lipopolysaccharide (LPS, 5mg/kg, ip). PTX was injected via the tail vein 1 minute after LPS challenge in five doses of 6.25, 12.5, 25, 50 and 100 mg/kg. NF-kappa B activation in the intestine was investigated with electrophoretic mobility shift assay (EMSA). Intestinal tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured with enzyme-linked immunosorbance assays (ELISA),and all the measurements about NF-kappa B,TNF-α, IL-6 and IL-10 were done at 2 hour after endotoxin injection. Results LPS elevated production of TNF-α, IL-6, IL-10 and enhanced NF-kappa B activation in the intestine. At the 5 dosages studied, PTX reduced NF-kappa B activation and TNF-α, IL-6 production.The greatest effects were observed in a dose of 50 mg/kg for NF-kappa B,TNF-α and IL-6, and 25 mg/kg for IL-10.Conclusion PTX induced a dose dependent suppression on proinflammatory cytokines production such as TNF-α and IL-6 in the intestine but enhanced endotoxin-induced IL-10 release. The suppressive effect of proinflammatory cytokines might act through inhibiting NF-kappa B.