法舒地尔对脂多糖诱导急性肺损伤大鼠肺组织p38丝裂原活化蛋白激酶激活的影响

目的观察法舒地尔对脂多糖(LPS)诱导的急性肺损伤(ALI)大鼠肺组织p38MAPK磷酸化激活的影响。方法 45只雄性SD大鼠随机分为三组:对照组(NS组,n=15)、脂多糖组(LPS组,n=15)及法舒地尔干预组(FAS组,n=15),LPS组和FAS组采用股静脉注射LPS(5 mg/kg)建立ALI模型,FAS组在LPS注射前30 min腹腔注射法舒地尔(10 mg/kg)。造模后3 h、6 h、12 h观察肺组织病理形态学改变,免疫组织化学及Western Blot法检测肺组织p-p38MAPK的表达。结果造模后LPS组各时间点肺组织p-p38MAPK的表达较NS组明显增加(P<0.05),与LPS组相比,FAS组各时间点p-p38MAPK的表达明显减少(P<0.05)。光镜显示LPS组病理形态学改变明显,而FAS组则明显减轻。结论法舒地尔可明显抑制脂多糖诱导的急性肺损伤大鼠肺组织p38MAPK的磷酸化激活,减轻脂多糖诱导的大鼠肺损伤程度。

The effect of fasudil on activation of p38MAPK in lung tissue of acute lung injury rats induced by lipopolysaccharide

Objective To investigate the potential effects of fasudil on phosphorylate activation of p38MAPK in lung tissue of acute lung injury（ALI）rats induced by lipopolysaccharide.Methods A total of 45 male SD rats were randomly divided into three groups：NS group（n=15）,LPS group（n=15） and FAS group（n=15）.ALI was induced by injecting LPS intravenously（5 mg/kg） in LPS group and FAS group.The FAS group was intraperitoneal injected with fasudil（10 mg/kg） thirty minutes before LPS injection.At 3 h,6 h,12 h after LPS injection,the pathomorphism changes of lung tissue were observed,and the expressions of p-p38MAPK protein in lung tissue were examined by immunohistoehemistry and Western Blot in all the rats.Results The pulmonary expressions of p-p38MAPK protein increased obviously in LPS group（P0.05）.Meanwhile,lower levels of p-p38MAPK protein were found in FAS group than those in LPS group at all time points（P0.05）.The pathological changes were more obvious in LPS group than those in FAS group.Conclusion Fasudil could attenuate the degree of acute lung injury of rats induced by LPS,which may be related to its effect in inhibiting the phosphorylate activation of p38MAPK in lung tissue.