天津医药

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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

王艳蕾1,蔡庆艳1,2,景友玲3,崔国金3,刘敏4,张凤宇5   

  1. 1. 河北联合大学
    2.
    3. 华北煤炭医学院
    4. 唐山市中医医院
    5. 唐山市丰润区人民医院
  • 收稿日期:2010-12-30 修回日期:2011-04-25 出版日期:2011-10-15 发布日期:2011-10-15
  • 通讯作者: 王艳蕾

Effects of sodium aescinate on p38 mitogen-activated protein kinase signal transduction pathway in lung injury induced by intestinal ischemia reperfusion

  • Received:2010-12-30 Revised:2011-04-25 Published:2011-10-15 Online:2011-10-15
  • Contact: WANG Yan-Lei

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摘要： 摘要 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：SD大鼠24只，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；模型组在用无创伤血管夹夹闭SMA，阻断该动脉血运1 h后松夹，恢复血流后观察1h，造成肠IR模型；治疗组于缺血前、再灌前、再灌后30 min尾静脉推注七叶皂苷钠0.9 ?g/g。测量各组肺表面活性物质卵磷脂（PC）、总磷脂（TPL）及肺湿/干比(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）模型组血浆和肺组织XOD、MPO活性及MDA含量均高于对照组和治疗组；治疗组血浆和肺组织XOD、MPO活性及MDA含量均高于对照组，差异均有统计学意义（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。

关键词: 再灌注损伤, 七叶素, p38丝裂原活化蛋白激酶类, 呼吸窘迫综合征, 成人, 卵磷酯类, 磷脂类, 黄嘌呤氧化酶

Abstract: Abstract Objective: To explore the effects of sodium aescinate(SA) on p38 mitogen-activated protein kinase(p38MAPK) signal transduction pathway in lung injury induced by intestinal ischemia reperfusion. Methods: 24 SD rats were randomly divided into three groups:sham group,IR group,treatment group. In sham group ,superior mesenteric artery was separated only; Models of intestinal IR injury were estabished with clamping of the superior mesenteric artery for 1h and then clamping was relieved for 1h. In treatment group, SA(0.9μg/g) was injected through tail vein before ischemia, before reperfusion and after reperfusion 30min respectively. Pulmonary surfactant(PS), lung wet/dry weight ratio, xanthine oxidase(XOD), malondialdehyde(MDA) , myeloperoxidase (MPO) in plasma and lung tissue were measured, as well as the expression levels of p38MAPK and Bax proteins in lung tissue were examined using immunohistochemical method. Results: (1) In IR group, PS were significently decreased than that in sham group(P<0.01), and while lung wet/dry weight ratio were significantly increased than that in sham group(P<0.01), The above-mentioned indexes of treatment group were obviously ameliorated in comparison with IR group(P<0.01).(2) The activity of ,XOD,MPO and the content of MDA in in plasma and lung tissue were significently increased in IR group than that in sham group (P<0.01). The above-mentioned indexes of treatment group were obviously lower in comparison with IR group(P<0.01). (3)The protein expression level 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 MDA,MPO and the expression levels of Bax proteins in lung tissue were positively correlated with the expression levels of p38MAPK proteins(P<0.01). Conclusion: Sodium aescinate can prevent the lung injury induced by intestinal ischemia reperfusion(IR) ,such protective effect may be related to the adjustment of the p38MAPK signal transduction pathway by inhibiting the generation of oxygen free radicals and activation of neutrophils and then prevent apoptosis.

Key words: reperfusion injury escin p38 mitogen-activated protein kinases respiratory distress syndrome, adult lecithins phospholipidsxanthine oxidase malondialdehyde, 黄嘌呤氧化酶