地塞米松对内毒素性肺损伤大鼠肺泡巨噬细胞丝裂原激活的蛋白激酶磷酸酶-1表达的影响

目的 探讨地塞米松(dexamethason,DEX)对急性肺损伤(acute lung injury,ALI)大鼠肺泡巨噬细胞(alveolar macrophage,AM)中丝裂原激活的蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1,MKP-1)的影响,以及AM中MKP-1表达在内毒素性肺损伤中的可能作用.方法 大鼠尾静脉注射内毒素建立急性肺损伤模型.Western blot法检测肺巨噬细胞的p38MAPK,磷酸化p38MAPK,MKP-1含量变化;ELISA法检测细胞培养上滴液中TNF-α,IL-6的含量改变.结果 脂多糖可使细胞培养上滴液中,TNF-α和IL-6的表达增加(P<0.05),DEX可以部分逆转上述作用(P<0.05).且可诱导内毒素肺损伤模型AM中MKP-1表达增加(P<0.05).结论 脂多糖促进TWF-α和IL-6的表达,可能是急性肺损伤肺内炎症损害的启动和促进因素;DEX可能通过抑制TNF-α和1L-6的表达并且增加AM中MKP-1的含量,进而抑制p38MAPK,发挥抗炎作用.

Devamethason mediate mitogen-activated protein kinase phosphatase-1 in alveolar macrophage in acute lung injury

Objective In the present study, we have addressed to investigate the effect of dexamethasone on expression of mitogen-activated protein kinase phosphatase-I (MKP-1) in rat alveolar macrophages with lipopolysaceharide (LPS) -induced acute lung injury, as well as the possible role of the expression of MKP-1 in LPS-induced acute lung injury. Methods Acute lung injury model was made by injection of LPS in rat tail vein. The content of p38MAPK, phosphorylation p38MAPK; as well as MKP-1 were detected by Western blot method; TNF-α and IL-6 levels in cell culture supernatant were deetected by ELISA method. Results LPS up-regulated the expression of TNF-α and IL-6 in cell culture supernatant (P < 0. 05). Dexamethasone partly reversed the above role (P < 0.05). and also induced the up-regulation of MKP-1 in LPS-induced ALI (P < 0. 05). Conclusion LPS can promote the expression of TNF-α and IL-6, which may play a cause and start role on inflammation in ALI. Dexmethasone may up-regulate the content of MKP-1 in AM and inhibit the expression of TNF-α and IL-6; thereby inhibiting the activation of p38MAPK, and playing the role of anti-inflammation in ALI.