不同剂量辛伐他汀对内毒素ALI大鼠肺组织XIAP表达水平的影响

Effect of Simvastatin on the expression of XIAP of lung tissues in rats with acute lung injury induced by endotoxin

目的 探讨不同剂量辛伐他汀对内毒素急性肺损伤（ALI）大鼠肺组织XIAP表达水平及肺损伤程度的影响.方法 将SD大鼠随机分五组,对照组予以注射生理盐水,余四组均注射5 mg/kg内毒素制备ALI大鼠模型,其中除LPS组外,Sta1、Sta2、Sta3组再同时分别给予10、20、40 mg/kg辛伐他汀进行干预.分别在注射内毒素后6、12、24 h处死大鼠,应用免疫组织化学、RT-PCR等方法观察各组不同时点肺组织病理形态学变化及肺组织XIAP表达水平.结果 与对照组比较,LPS、Sta1、Sta2和Sta3组大鼠各时间点肺组织中XIAP表达水平均明显增加（P〈0.05）.在各时间点的大鼠肺组织中XIAP表达水平比较中,Sta1组虽较LPS组降低,但差异无统计学意义（P〉0.05）;而Sta2、Sta3组较LPS、Sta1组均明显下降（P〈0.05）;Sta2组和Sta3组比较差异无统计学意义（P〉0.05）.上述结果与肺病理损伤程度变化相吻合.结论 辛伐他汀可显著降低内毒素致ALI大鼠肺组织XIAP表达水平和减轻ALI,推荐20 mg/kg为防治内毒素ALI的最佳剂量.

Objective To investigate the effect of Simvastatin on the expression of XIAP of lung tissues in rats with acute lung injury （ALI） induced by endotoxin, and the possibly protective effect of Simavastatin against ALI. Methods The SD rats were randomly divided into five groups： Control group, Stal group, Sta2 group, Sta3 group and LPS group. 5 mg/kg endotoxin was injected to induce ALI rats models. ALI rats were administrated with 10 mg/kg （Stal group）, 20 mg/kg （Sta2 group）, 40 mg/kg （Sta3 group） Simavastatin or without Simavastatin （LPS group）. The rats in control group were injected with saline. The pathomorphological changes and the expression of XIAP in lung tissue at 6 h, 12 h, 24 h after injection were analyzed by immunohistochemistry assay and reverse transcription polymerase chain reaction, etc. Results Compared to the control group, the expressions of XIAP of lung tissues in LPS group, Stal group, Sta2 group, Sta3 group rats were significantly increased （P 〈 0. 05） at different time points. When the levels of XIAP in different groups were compared between different time points, it was found that the levels of XIAP in Stal group were decreased compared to those in LPS group, but the differences were no significant （P 〉 0.05 ） ; the levels of XIAP in Sta2 and Sta3 group were significantly decreased compared to those in LPS and Stal group （P 〈 0.05 ）, but the levels of XIAP were no significant difference between Sta2 group and STa3 group （P 〈 0.05 ）. These results were consistent with the degree of pathological lesion of lung tissue. Conclusion Simvastatin can decrease the expression of XIAP of lung tissues in rats with acute lung injury caused by endotoxin and relieve the degree of lung injury, 20 mg/kg Simvastatin is recommended as the optimum dose for preventing and treating endotoxin -ALI.