AIM; To observe the role of p38 mitogen - activated protein kinase ( p38 MAPK) - heat - shock protein 27 ( HSP27) signaling pathway in lipopolysaccharide - induced acute lung injury ( ALI) in rats. METHODS: Wistar rats were randomly divided into control group, ALI group and ALI + SB203580 group. After the experimental model was established, the rats were sacrificed. The pathological changes of the lung and the changes of F - actin and G - actin in the endothelial cells were observed. The ratio of wet weight to dry weight (W/D) of the lung tissues was measured. The protein levels in bronchoalveolar lavage fluid ( BALF) were detected. The levels of IL -6 and TNF - a in serum and BALF were tested. The concentrations of p - p38 and p - HSP27 in the lung were determined. RESULTS: In ALI group, the protein levels in BALF and W/D ratio of the lung increased significantly at 2 h. The levels of TNF - a and IL - 6 in serum and BALF began to increase at 2 h, which had significant difference as compared with control group. Aleolar epithelial swelling, alveolar walls widening, alveolar interstitial and cavity edema, and the exudation of alveolar inflammation cells, red blood cells and protein were observed in ALI group. The protein levels in BALF and W/D ratio of the lung in ALI + SB203580 group were much less than those in ALI group. The exudation of alveolar inflammation cells, red blood cells and protein, and the interstitial and alveolar edema in ALI + SB203580 group alleviated as compared with ALI group. The ex-pression of p - p38 MAPK and p - HSP27 in the lung at 2 h in ALI group was higher than that in control group. F - actinrnexpression in ALI group obviously increased than that in control group at time points of 0 h and 8 h. Compared with ALI group, the expression of p - HSP27 and F - actin in ALI + SB203580 group was reduced. CONCLUSION: Lipopolysac-charide activates p38 MAPK - HSP27 signaling pathway and induces lung injury. Blockage of p38 MAPK - HSP27 signa-ling pathway may reduce lung injury.%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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