Resveratrol reduces acute lung injury in a LPS-induced sepsis mouse model via activation of Sirt1 (Retracted Article)
Resveratrol reduces acute lung injury in a LPS-induced sepsis mouse model via activation of Sirt1 (Retracted Article)
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DOI：
10.3892/mmr.2013.1444
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发表时间：
2013-06-01
影响因子：
3.4
通讯作者：
Wu, Qinghua
中科院分区：
文献类型：
--
作者：
Li, Tongxun;Zhang, Jinglan;Wu, Qinghua
脓毒症时发生的急性肺损伤(ALI)几乎使患者的死亡率增加一倍。目前的治疗策略的疗效很低，因为治疗通常是在症状出现后开始的。炎症是自身免疫性疾病的主要机制之一，也是脓毒症的共同特征。因此，抑制炎症反应是治疗脓毒症的重要机制。Sirtuin 1(sirtuin 1，Sirt1)已被证明在炎症的调节中发挥作用。白藜芦醇是一种有效的Sirt1激活剂，具有抗炎特性。然而，白藜芦醇在脓毒症期间治疗ALI中的作用尚不完全清楚。本研究采用小鼠脓毒症模型，研究了Sirt1在脂多糖诱导的TC-1细胞系中的抗炎作用及其对ALI的治疗作用。在脓毒症小鼠模型和TC-1细胞系中，脂多糖诱导基质金属蛋白酶-9、白介素1-β、白介素6和诱导型一氧化氮合酶表达上调，白藜芦醇呈剂量依赖性抑制这些促炎分子的过度表达。白藜芦醇可减轻脂多糖诱导的脓毒症小鼠的肺水肿。此外，白藜芦醇改善了脓毒症小鼠模型的肺功能，减少了病理改变。RNA干扰下调Sirt1基因后，TC-1细胞对内毒素刺激的敏感性增加，白藜芦醇的抗炎作用减弱。这些结果表明，白藜芦醇通过Sirt1抑制内毒素诱导的ALI和炎症反应，提示Sirt1是调节内毒素诱导的ALI和炎症反应的有效靶点。本研究为脓毒症时ALI的治疗提供了新的思路。
The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits anti-inflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the anti-inflammatory role of Sirt1 in the lipopolysaccharide (LPS)-induced TC-1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)-1 beta, IL-6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC-1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dose-dependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC-1 cells to LPS stimulation and diminished the anti-inflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPS-induced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPS-induced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis.