七叶皂苷钠对肠缺血再灌注肺损伤p38MAPK信号转导通路的影响

Effects of Sodium Aescinate on p38MAPK Signal Transduction Pathway in Lung Injury Induced by Intestinal Ischemia Reperfusion

目的:探讨七叶皂苷钠对肠缺血再灌注(IR)肺损伤p38MAPK信号转导通路的影响。方法:24只SD大鼠随机均分为3组。对照组只分离出肠系膜上动脉(SMA),不夹闭SMA;模型组用无创伤血管夹夹闭SMA,阻断该动脉血运1h后松夹,恢复血流后观察1h,造成肠IR模型;治疗组于缺血前、再灌注前、再灌注后30min尾静脉推注七叶皂苷钠0.9μg/g。测量各组肺表面活性物质卵磷脂(PC)、总磷脂(TPL)及肺湿/干质量比(W/D),测量血浆和肺组织中黄嘌呤氧化酶(XOD)、丙二醛(MDA)及髓过氧化物酶(MPO)水平,采用免疫组化法检测各组肺组织中p38MAPK和Bax蛋白的表达水平。结果:(1)模型组和治疗组的肺组织PC、TPL含量均低于对照组,肺W/D高于对照组;治疗组的肺组织PC、TPL含量高于模型组,肺W/D低于模型组,差异均有统计学意义(P<0.01)。(2)血浆和肺组织XOD、MPO活性及MDA含量模型组高于对照组和治疗组,且治疗组高于对照组,差异均有统计学意义(P<0.05或P<0.01)。(3)模型组肺组织p38MAPK和Bax蛋白的表达水平明显高于对照组和治疗组(P<0.01)。(4)模型组肺组织MPO、MDA及Bax蛋白表达水平与肺组织细胞p38MAPK蛋白表达水平呈正相关(r分别为0.897、0.902和0.912)。结论:七叶皂苷钠可减轻肠IR肺损伤,其机制可能是通过抑制氧自由基的产生、白细胞的活化来调控p38MAPK信号转导通路,从而抑制肺组织细胞的凋亡。

Objective： To explore the effects of sodium aescinate （SA） on p38 mitogen-activated protein kinase （MAPK） signal transduction pathway in lung injury induced by intestinal ischemia reperfusion（IR）. Methods： Twenty-four SD rats were randomly divided into three groups： sham group, IR group and treatment group. In sham group, superior mesen- teric artery was separated only. Models of intestinal IR injury were established with clamping of the superior mesenteric artery for lh and then the clamping was relieved for lh. In treatment group, SA （0.9 t^g/g） was injected through tail vein 30 min be- fore ischemia, before reperfusion and after reperfusion respectively. The values of phosphatidyl choline（PC）, total phospholip- ids （TPL） and lung wet/dry weight ratio （W/D） were measured. The levels of xanthine oxidase （XOD）, malondialdehyde （MDA） and myeloperoxidase （MPO） were also detected in rats of groups. The expression of p38MAPK and Bax proteins in lung tis- sues were examined using immunohistochemical method. Results： （1） The levels of PC and TPL were significantly lower, and the value of W/D was higher, in IR group and treatment group than that in sham group （P 〈 0.01）. The values of PC and TPL was significantly higher, and the W/D was lower, in treatment group than that of IR group （P 〈 0.01）. （2） The activity of XOD, MPO and the content of MDA in plasma and lung tissues were significantly increased in IR group than those of sham group and treatment group （P 〈 0.01）, and was higher in treatment group than that of sham group（P 〈 0.05 or P 〈 0.01）. （3）The pro- tein expression levels of p38MAPK and Bax were significantly increased in IR group than that in sham group and treatment group （P 〈 0.01）. （4）The correlation analysis indicated that MPO, MDA and the expression levels of Bax proteins were positively correlated with the expression levels of p38MAPK proteins of IR group （P 〈 0.01）. Conclusion： Sodium aescinate can prevent the lunz injury induced bv intestinal IR, which may be related to the adiustment of the p38MAPK signal transduction