一氧化碳减轻脂多糖诱导的大鼠小肠损伤与p38 MAPK磷酸化水平的关系

目的：观察低浓度一氧化碳（CO）吸入和腹腔给予对脂多糖（LPS）诱导大鼠小肠损伤的作用及作用过程中丝裂原活化蛋白激酶p38（p38 MAPK）磷酸化水平的变化。方法：6组SD大鼠静脉注入5mg／kg体质量IPS或等容量生理盐水;1h后,对照及LPS注入组吸入室内空气,CO吸入及LPS注入＋CO吸入组吸入体积分数为2．5×10^-4CO．CO腹腔及LPS注入＋CO腹腔组腹腔通入体积分数为2．5×10^-4CO。观察1、3、6h后放血处死,取回盲部上小肠,酶联免疫吸附法测定血小板活化因子（PAV）及细胞间黏附分子-1（ICAM-1）水平;光镜观察组织形态学变化;蛋白印迹法测定p38 MAPK磷酸化水平。结果：LPS注入组PAF、ICAM-1及p38 MAPK磷酸化水平显著高于相应时间点的对照、CO吸入及CO腹腔组（P均〈0．01）;组内各时间点比较,差异无统计学意义。与相应时间点的LPS注入组比较,LPS注入＋CO吸入及LPS注入＋CP腹腔组的PAF和ICAM-1明显降低（P均〈0．05）,但p38 MAPK磷酸化水平进一步增高（P均〈0．05）;此两组间及两组内各时间点比较,差异无统计学意义。结论：低浓度CO吸入和腹腔给予以非时间依赖方式下调LPS诱导的大鼠小肠PAF、ICAM-1表达而起相似的保护作用;p38 MAPK信号转导通路可能参与了这一过程。

Effects of p38 mitogen-activated protein kinase in protection of carbon monoxide against lipopolysaccharide induced rat small intestine injury

To investigate the effects of low concentration carbon monoxide （CO） inhalation or intraperitoneal infusion on lipopolysaccharide （LPS） induced rat small intestine injury and to detect the roles of p38 mitogen-activated protein kinase（MAPK） pathway during CO administration. Methods： SD rats with small intestine injury induced by 5 mg/kg LPS intravenous injection were challenged by room air, 2.5 × 10^-4（v/ V） CO inhalation or intraperitoneal infusion for 1 h, 3 h and 6 h differendy. Then all animals were sacrificed, and the ileum tissues were homogenized for determination the levels of platelet activator factor（PAF） and intercellular adhesion molecule-1 （ICAM-1） with enzyme-lined immunosorbent assay, the pathology with light microscope, and the pbosphorylated p38 MAPK expression with Western blot. Results： Compared with either control, CO inhalation or intraperitoneal infusion group at the same time point, the levels of PAF, ICAM-1 and the phosphorylated p38 MAPK of LPS group were increased （all P 〈 0.01 ）, but there were no statistics differences at the different time point of this group. PAF and ICAM-1 in both LPS injection ＋ CO inhalation group and LPS injection ＋ CO intraperitoneal infusion group were significantly lower than the corresponding value in LPS injection group at the same time point（all P 〈 0.05）, while the expression of phosphorylated p38 MAPK was further up-regulated than that of LPS injection group（ P 〈 0.05）. However, there were no significant differences in these parameters between LPS injection ＋ CO inhalation group and LPS injection ＋ CO intraperitoneal infusion group. Conclusion： Low concentration CO inhalation and intraperitoneal infusion exerts the similar protection against LPS induced rat small intestine injury via down-regulating PAF and ICAM-1 expression. This may involve the p38 MAPK pathway.