Medical Intensive Care Unit, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.
Respir Care. 2011 Aug;56(8):1156-63. doi: 10.4187/respcare.00770. Epub 2011 Mar 9.
3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have several pleiotropic effects, including anti-inflammatory properties, and are reported to improve endothelial functions. Pathophysiologically, acute lung injury (ALI) is caused by a severe inflammatory response and endothelial dysfunction.
To investigate the effects of simvastatin (an HMG-CoA reductase inhibitor) on oxidative stress and lung histopathology in 2 murine models of ALI, induced by oleic acid and endotoxin.
The mice were randomly divided into 2 groups: one received 2 mg/kg/d intraperitoneal simvastatin for 15 days. Then the groups were further divided into 3, which received saline, oleic acid, or endotoxin. Four hours after inducing ALI we obtained lung samples for histopathology analysis, myeloperoxidase, glutathione, and malondialdehyde measurement, and blood samples for malondialdehyde measurement.
Endotoxin and oleic acid lung injury increased tissue myeloperoxidase (P = .009 for both), decreased tissue glutathione (P = .02 and P = .009, respectively), and increased tissue malondialdehyde (P = .009 for both), compared to the control group. Simvastatin decreased myeloperoxidase only in the oleic acid group (P = .01). Simvastatin increased glutathione (P = .005 and P = .003, respectively) and lowered malondialdehyde in both the endotoxin and oleic acid groups (P = .003 for both). Histopathology revealed that simvastatin protected the lung tissue in both ALI models, but the protection was greater in the endotoxin group.
Pretreatment with simvastatin decreased the severity of ALI in oleic acid and endotoxin ALI models, by decreasing inflammation and oxidative stress.
3-羟-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂具有多种多效性，包括抗炎特性，并据报道可改善内皮功能。从病理生理学上讲，急性肺损伤（ALI）是由严重的炎症反应和内皮功能障碍引起的。
研究辛伐他汀（一种 HMG-CoA 还原酶抑制剂）对油酸和内毒素诱导的 2 种 ALI 小鼠模型的氧化应激和肺组织病理学的影响。
将小鼠随机分为 2 组：一组接受 2 mg/kg/d 辛伐他汀腹腔注射治疗 15 天。然后，这两组又进一步分为 3 组，分别接受生理盐水、油酸或内毒素。在诱导 ALI 后 4 小时，我们获取肺组织样本进行组织病理学分析、髓过氧化物酶、谷胱甘肽和丙二醛测量以及血液样本的丙二醛测量。
与对照组相比，内毒素和油酸肺损伤均增加了组织髓过氧化物酶（P =.009，均），降低了组织谷胱甘肽（P =.02 和 P =.009，分别），并增加了组织丙二醛（P =.009，均）。辛伐他汀仅降低油酸组的髓过氧化物酶（P =.01）。辛伐他汀增加了谷胱甘肽（P =.005 和 P =.003，分别），并降低了内毒素和油酸组的丙二醛（P =.003，均）。组织病理学检查显示，辛伐他汀在两种 ALI 模型中均能保护肺组织，但在内毒素组的保护作用更强。
辛伐他汀预处理可通过降低炎症和氧化应激来减轻油酸和内毒素性 ALI 模型中 ALI 的严重程度。
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