Sepsis-induced acute lung injury (ALI) is milder in diabetic rats and correlates with impaired NFkB activation.
Sepsis-induced acute lung injury (ALI) is milder in diabetic rats and correlates with impaired NFkB activation.
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DOI：
10.1371/journal.pone.0044987
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jancar S
中科院分区：
文献类型：
--
作者：
Filgueiras LR Jr;Martins JO;Serezani CH;Capelozzi VL;Montes MB;Jancar S
急性肺损伤（ALI）是由于对肺部的直接损伤或继发性全身炎症反应（例如败血症）而发生的。有临床证据表明，糖尿病患者中直接损伤引起的 ALI 的发生率和严重程度较低。在本研究中，我们研究了同样的情况是否会继发于脓毒症而发生在 ALI 中，以及所涉及的分子机制。四氧嘧啶诱发雄性 Wistar 大鼠糖尿病，盲肠结扎穿刺手术 (CLP) 诱发脓毒症。六小时后，在支气管肺泡灌洗中检查肺部是否有水肿和细胞浸润。体外培养肺泡巨噬细胞 (AM)，用于分析 NFκB 磷酸化的 IκB 和 p65 亚基以及 MyD88 和 SOCS-1 mRNA。糖尿病大鼠比非糖尿病大鼠更容易患败血症。在非糖尿病大鼠中，肺部出现水肿、白细胞浸润和 COX2 表达增加。在糖尿病大鼠中，这些炎症事件明显不那么强烈。为了了解为什么糖尿病大鼠更容易患脓毒症，但会发展出较轻的 ALI，我们检查了脓毒症动物 AM 中 NFκB 的激活情况。在非糖尿病大鼠中，IκB 和 p65 亚基的磷酸化在脓毒症诱导 6 小时后发生，而在糖尿病大鼠中则没有发生。此外，与非糖尿病大鼠的AM相比，糖尿病大鼠的AM中MyD88 mRNA的表达较低，而SOCS-1 mRNA的表达升高。这些结果表明，糖尿病大鼠中脓毒症继发的 ALI 较轻，这与 NFκB 激活受损、SOCS-1 增加和 MyD88 mRNA 减少相关。
Acute lung injury (ALI) develops in response to a direct insult to the lung or secondarily to a systemic inflammatory response, such as sepsis. There is clinical evidence that the incidence and severity of ALI induced by direct insult are lower in diabetics. In the present study we investigated whether the same occurs in ALI secondarily to sepsis and the molecular mechanisms involved. Diabetes was induced in male Wistar rats by alloxan and sepsis by caecal ligation and puncture surgery (CLP). Six hours later, the lungs were examined for oedema and cell infiltration in bronchoalveolar lavage. Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA. Diabetic rats were more susceptible to sepsis than non-diabetics. In non-diabetic rats, the lung presented oedema, leukocyte infiltration and increased COX2 expression. In diabetic rats these inflammatory events were significantly less intense. To understand why diabetic rats despite being more susceptible to sepsis develop milder ALI, we examined the NFκB activation in AMs of animals with sepsis. Whereas in non-diabetic rats the phosphorylation of IκB and p65 subunit occurred after 6 h of sepsis induction, this did not occur in diabetics. Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats. These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.
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DOI：
10.1186/cc7717
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Esper AM;Moss M;Martin GS
通讯作者：
Martin GS
影响因子：
7.7
作者：
Fernandez-Valverde SL;Taft RJ;Mattick JS
通讯作者：
Mattick JS
影响因子：
--
作者：
Geerlings, SE;Hoepelman, AIM
通讯作者：
Hoepelman, AIM
影响因子：
3.3
作者：
Menezes, SLS;Bozza, PT;Rocco, PRM
通讯作者：
Rocco, PRM
影响因子：
3.1
作者：
Salomao, Reinaldo;Martins, Paulo Sergio;Rigato, Otelo
通讯作者：
Rigato, Otelo