Role of p38 MAPK-HSP27 signaling pathway in rat acute lung injury induced by lipopolysaccharide
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF PATHOPHYSIOLOGY
- Issue:
- 11
- DOI:
- 10.3969/j.issn.1000-4718.2012.11.005
- Key Word:
- 急性肺损伤;细胞因子类;p38丝裂原激活蛋白激酶;热休克蛋白27;F-肌动蛋白
Abstract： 目的:观察p38丝裂原激活蛋白激酶(p38 MAPK)-热休克蛋白27(HSP27)信号通路在急性肺损伤病理过程中的变化规律.方法:健康雄性Wistar大鼠(300～320 g)随机分成正常对照组(A组)、急性肺损伤组(B组)及急性肺损伤+SB203580组(C组).通过腹腔注射内毒素建立急性肺损伤大鼠模型,分别于实验开始后的0、2、4、6、8 h处死各组大鼠.检测支气管肺泡灌洗液(BALF)白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)及BALF中蛋白含量.苏木素-伊红(HE)染色检查肺组织病理变化及免疫荧光方法检测内皮细胞内F-actin和G-actin,计算肺湿干重比值(W/D).检测肺组织中磷酸化p38 MAPK(p-p38 MAPK)及磷酸化HSP27(p-HSP27)的含量.结果:B组在实验后2 h BALF中蛋白水平和肺W/D开始明显增加,给予内毒素后8 h肺泡上皮肿胀,肺泡壁增宽,肺泡间质和肺泡腔水肿明显,肺泡内炎症细胞、红细胞和蛋白渗出明显增多,表现出急性肺损伤的病理改变.在给予了p38 MAPK抑制剂SB203580后的C组BALF中蛋白水平及肺W/D分别比B组明显减少,肺泡内炎症细胞、红细胞和蛋白渗出、间质与肺泡水肿均较B组减轻.B组均在实验后2 h血清及BALF中TNF-α和IL-6的浓度开始增加,p-p38 MAPK及p-HSP27的肺内表达开始增加,与A组相比有显著差异.B组实验后8 h的F-actin的表达明显比A组实验后0 h及8 h的增加,给予p38 MAPK抑制剂SB203580的C组肺p-HSP27和F-actin的表达分别比B组明显减少.结论:内毒素可以通过激活p38 MAPK-HSP27信号通路引起急性肺损伤;阻断该信号通路可以减轻肺损伤.
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