The effect of rosuvastatin in a murine model of influenza A infection.
The effect of rosuvastatin in a murine model of influenza A infection.
复制标题
DOI：
10.1371/journal.pone.0035788
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mutlu GM
中科院分区：
文献类型：
--
作者：
Radigan KA;Urich D;Misharin AV;Chiarella SE;Soberanes S;Gonzalez A;Perlman H;Wunderink RG;Budinger GR;Mutlu GM
HMG-CoA还原酶抑制剂（如瑞舒伐他汀）可能具有免疫调节和抗炎作用，可降低甲型流感病毒感染的严重程度。我们假设瑞舒伐他汀可以减少病毒复制，减轻肺损伤，并改善小鼠感染甲型流感后的死亡率。从A//Udorn/72 [H3 N2]或A/WSN/33 [H1N1]甲型流感病毒（1×105 pfu/小鼠）感染前3天开始，C57 Bl/6小鼠每天接受补充在饲料（或对照饲料）中的瑞舒伐他汀（10 mg/kg/天）给药。使用空斑试验检查瑞舒伐他汀对体外病毒复制和感染小鼠肺中病毒复制的影响。在第1、2、4和6天，我们测量了支气管肺泡灌洗液（BAL）中的分类细胞计数、蛋白质和细胞因子、肺损伤的组织学证据和湿干比。我们还记录了每日体重和死亡率。瑞舒伐他汀给药对感染后甲型流感病毒的清除无影响。瑞舒伐他汀和对照给药小鼠的体重减轻、肺部炎症和肺损伤严重程度相似。在感染甲型流感病毒（A/WSN/33）的小鼠中，死亡率不受瑞舒伐他汀给药的影响。他汀类药物在体外不改变甲型流感病毒的复制，也不增强其在体内从肺部的清除。他汀类药物既不能减轻甲型流感引起的肺损伤的严重程度，也不能降低甲型流感相关的死亡率。我们的数据表明，HMG CoA还原酶抑制剂与脓毒症和肺炎患者结局改善之间的相关性并不归因于其对甲型流感感染的影响。
HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza A infection in mice. C57Bl/6 mice were treated daily with rosuvastatin (10 mg/kg/day) supplemented in chow (or control chow) beginning three days prior to infection with either A//Udorn/72 [H3N2] or A/WSN/33 [H1N1] influenza A virus (1×105 pfu/mouse). Plaque assays were used to examine the effect of rosuvastatin on viral replication in vitro and in the lungs of infected mice. We measured cell count with differential, protein and cytokines in the bronchoalveolar lavage (BAL) fluid, histologic evidence of lung injury, and wet-to-dry ratio on Day 1, 2, 4, and 6. We also recorded daily weights and mortality. The administration of rosuvastatin had no effect on viral clearance of influenza A after infection. Weight loss, lung inflammation and lung injury severity were similar in the rosuvastatin and control treated mice. In the mice infected with influenza A (A/WSN/33), mortality was unaffected by treatment with rosuvastatin. Statins did not alter the replication of influenza A in vitro or enhance its clearance from the lung in vivo. Statins neither attenuated the severity of influenza A-induced lung injury nor had an effect on influenza A-related mortality. Our data suggest that the association between HMG CoA reductase inhibitors and improved outcomes in patients with sepsis and pneumonia are not attributable to their effects on influenza A infection.