Regulation of p38 mitogen-activated protein kinase signal pathway-mediated thrombocytopenia in septic mice

Abstract

Objective To discuss whether p38 mitogen-activated protein kinase (p38MAPK) signal pathway participates in the modulation of thrombocytopenia in septic mice. Methods Mice models of sepsis were established by intraperitoneal injection of lipopolysaccharide (LPS) in the lethal dose. Sixty mice were randomly divided into three groups: control group, sepsis group and the p38MAPK inhibitor group (SB203580 treatment group). Platelet counts, and the expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were detected continuously in the first four days. Twenty-four h after the injection of LPS, the morphological changes in platelets were observed, the expression of p-p38MAPK was detected, and platelet sequestration in the lung was examined through immunohistochemistry. Results The concentrations of IL-6 and TNF-α were higher in LPS group than in control group. In LPS group, large number of swelling and deformative platelets were observed, showing significant status of activation. The expression of phosphorylated p38MAPK (p-p38MAPK, ratio of band density was 0.603 1±0.032 5, P<0.01) in platelets and sequestration of platelets in the lung increased obviously in LPS group (mean density value was 206.18±5.14, P<0.05). Conclusion p38MAPK may play an important role in the activation of platelets. Inhibition of p38MAPK can reduce activation of platelets, sequestration of platelets in the lung, and finally prevent thrombocytopenia of septic mice. Key words: Sepsis; Platelet; p38 mitogen-activated protein kinase