法舒地尔对脂多糖诱导的大鼠急性肺损伤的影响
The effect of fasudil on the acute lung injury in rats induced by lipopolysaccharide
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摘要: 目的：探讨法舒地尔通过RhoA/ROCK(Rho激酶)通路是否能减轻脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)。方法：18只Wistar健康大鼠随机分为对照组(NS组)、脂多糖组(LPS组)及法舒地尔干预组(FAS组)各6只；LPS组和FAS组采用小剂量LPS 1 mg/kg腹腔注射16 h后，气管内滴注LPS 3 mg/kg建立ALI模型。FAS组在腹腔注射LPS前30 min和气管滴注LPS后1 h给予腹腔注射法舒地尔10 mg/kg。于气管滴注LPS造模后，观察3 h后处死大鼠，通过HE染色观察各组肺组织形态学改变，测肺组织湿/干重比、丙二醛含量、髓过氧化物酶活性，反转录-聚合酶链反应及Western blot法检测肺组织匀浆中ROCK2(Rho激酶2)mRNA及蛋白的表达情况。结果：与NS组比较，LPS组肺组织病理形态学改变明显，FAS组较LPS组相比明显减轻；LPS组肺湿/干重比、丙二醛含量和髓过氧化物酶活性均较NS组明显增高(P0.01)，而FAS组较LPS组均有不同程度降低(P0.05~P0.01)；LPS组ROCK2 mRNA 表达较NS组明显增高(P0.01)，而FAS组与LPS组差异无统计学意义(P0.05)；LPS组ROCK2蛋白表达较NS组明显增高(P0.01)，而FAS组较LPS组表达水平降低(P0.05)。结论：法舒地尔通过RhoA/Rho激酶信号通路能够减轻LPS诱导的大鼠ALI。
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关键词:
- 肺损伤 /
- 法舒地尔 /
- 脂多糖 /
- RhoA/Rho激酶
Abstract: Objective:To investigate the effects of fasudil on the acute lung injury(ALI) in rats induced by lipopolysaccharide(LPS) through the RhoA/Rho kinase pathway.Methods:Eighteen wistar rats were randomly divided into control group,LPS group and fasudil(FAS) group(6 rats each group).The ALI model was established by intraperitoneal injection of LPS 1 mg/kg for 16 hours,and then endotracheal instillation of LPS 3 mg/kg.The fasudil 10 mg/kg was intraperitoneally injected into FAS group at 30 min before intraperitoneal injection of LPS and 1 hour after endotracheal instillation of LPS.The rats were sacrificed after 3 hours.The morphological changes of lung tissue in 3 groups were observed by HE staining,the ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in 3 groups were measured,and the ROCK2(Rho kinase 2) mRNA and protein expressions in 3 groups were detected by reverse transcription-polymerase chain reaction and Western blot,respectively.Results:Compared with the control group,the lung histopathology change in LPS group was obvious,and the lung histopathology change in FAS group was significantly gentler than that in LPS group.The ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in LPS group were significantly higher than those in control group(P0.01),but the indexes in FAS and LPS group were decreased to varying degrees(P0.05 to P0.01).Compared with the control group,the ROCK2 mRNA expression of lung in LPS group was increased(P0.01),but the difference of which had no statistical significance between FAS and LPS group(P0.05).Compared with the control group,the ROCK2 protein expression in LPS group was significantly increased(P0.01).Compared with the LPS group,the ROCK2 protein expression in FAS group was significantly decreased(P0.05).Conclusions:Fasudil can reduce the acute lung injury in rats induced by lipopolysaccharide through the RhoA/Rho kinase signal pathway.-
Key words:
- lung injury /
- fasudil /
- lipopolysaccharide /
- RhoA/Rho kinase
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