阿托伐他汀钙对脂多糖致急性肺损伤大鼠的作用研究

《阿托伐他汀钙对脂多糖致急性肺损伤大鼠的作用研究》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、目录1阿托伐他汀钙对脂多糖致急性肺损伤大鼠的作用研究„„„„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„11.2英文摘要„„„„„„„„„„„„„„„„„„„„„31.3前言„„„„„„„„„„„„„„„„„„„„„„„61.4材料与方法„„„„„„„„„„„„„„„„„„„„81.5结果„„„„„„„„„„„„„„„„„„„„„„„151.6讨论„„„„„„„„„„„„„„„„„„„„„„„261.7结论„„„„„„„„„„„„„„„„„„„„„„„341.8参考文献„„„„„„„„„„„„„„„„„„„„„351.9英汉缩略词对照表„„„„„„„„„„„„„„„„„3

2、92致谢„„„„„„„„„„„„„„„„„„„„„„„403他汀类药物在急性肺损伤中的作用（综述）„„„„„„„„„41阿托伐他汀钙对脂多糖致急性肺损伤大鼠的作用研究摘要目的：观察阿托伐他汀钙对脂多糖（LPS）所致急性肺损伤（ALI）大鼠肺组织中血管内皮生长因子（VEGF）、血栓素B2(TXB2）表达和肺泡灌洗液（BALF）中蛋白含量以及中性粒细胞（PMN）比例的影响。探讨阿托伐他汀钙在LPS所致急性肺损伤大鼠中的作用。方法：90只清洁级大鼠随机分为五组，分别为生理盐水(NS)组、LPS组、阿托伐他汀钙小剂量（S）组、阿托伐他汀钙中剂量（M）组、阿托伐他汀钙大剂量（L）组,各组大鼠18只

3、。NS组、LPS组予以NS灌胃，S组、M组和L组分别予以阿托伐他汀钙5mg/Kg/d、10mg/Kg/d、20mg/Kg/d灌胃，各组均连续给药14天，第15天后四组尾静脉注射LPS（6mg/Kg）稀释成1ml制备ALI大鼠模型，NS组尾静脉注射1ml的NS。各组分别于尾静脉注药后2h、4h、8h处死大鼠6只。比较肺组织病理学改变和肺损伤评分；检测各组大鼠肺湿/干重比(W/D)；考马斯亮蓝法测定BALF中蛋白含量同时监测BALF中PMN比例。实时荧光定量逆转录一聚合酶链反应（FQRT—PCR)检测肺组织VEGF、TXB2mRNA表达；免疫组织化学法测定肺组织中VEGF、TXB2的表达。结

4、果：①病理改变：NS组各时间点大鼠肺组织结构清晰、肺泡壁完整未发现炎性细胞浸润及肺泡间隔水肿。LPS组各时间点肺泡壁破裂，肺泡塌陷实变，肺泡隔及肺泡腔内出血，肺间质水肿、肺泡和间质内有大量中性炎细胞浸润。S组、M组、L组病理改变介于NS组和LPS组之间，以L组损伤最轻，M组其次，S组较重。各组以4h损伤最重，8h次之，2h最轻。②肺W/D、肺损伤评1分:各组大鼠2h、4h、8h均较NS组升高(P<0.05),S组、M组和L组在相同时间点较LPS组降低(P<0.05)，而M组在同一时间点较S组降低(P<0.05)，L组在同一时间点较M组降低(P<0.05)。③各组大鼠2h、4h、8hBAL

5、F中蛋白含量及PMN比例均较NS组升高(P<0.05),S组、M组和L组在相同时间点较LPS组降低(P<0.05),而M组在同一时间点较S组降低(P<0.05),L组在同一时间点较M组降低(P<0.05)。④各组大鼠2h、4h、8h肺组织VEGF、TXB2mRNA表达均较NS组升高(P<0.05),S组、M组和L组在相同时间点较LPS组降低(P<0.05)，同一时间点，M组较S组降低(P<0.05)，L组较M组降低(P<0.05)。结论：阿托伐他汀灌胃可降低LPS致ALI大鼠BALF中蛋白含量及PMN比例，其机制可能与肺组织VEGF、TXB2mRNA表达减少微血管通透性降低有关，从而达到

6、保护肺损伤的作用。关键词：阿托伐他汀钙；急性肺损伤；血栓素B2(TXB2)；血管内皮生长因子（VEGF）；荧光定量PCR2TheeffectofAtorvastatinCalciumonratswithacutelunginjuryinducedbyLipopolysaccharidesAbstractObjective:ToobservetheeffectofAtorvastatinCalciumontheexpressionoftheVEGFandThromboxaneB2(TXB2),andbronchoalveolarlavagefluid(BALF)proteincontent

7、aswellastheproportionofneutrophils(PMN)bylipopolysaccharide(LPS)-inducedacutelunginjury(ALI)inlungtissueofrats.ExploretheroleofatorvastatincalciuminratswithacutelunginjuryinducedbyLPS.Methods:healthymaleSDrats90wereran