Downregulation of Lung Toll-Like Receptor 4 Could Effectively Attenuate Liver Transplantation-Induced Pulmonary Damage at the Early Stage of Reperfusion.
Downregulation of Lung Toll-Like Receptor 4 Could Effectively Attenuate Liver Transplantation-Induced Pulmonary Damage at the Early Stage of Reperfusion.
复制标题
下调肺Toll样受体4可有效减轻肝移植引起的再灌注早期肺损伤
DOI：
10.1155/2015/383907
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发表时间：
2015
影响因子：
4.6
通讯作者：
Hei Z
中科院分区：
文献类型：
--
作者：
Chi X;Yao W;Zhang A;Ge M;Cai J;Zhou S;Xia Z;Luo G;Hei Z
急性肺损伤(ALI)是原位肝移植(OLT)的严重并发症，其发生机制尚不清楚。Toll样受体4(TLR4)被认为是介导炎症反应的关键受体。我们推测TLR4介导的肺部炎症可能参与了原位肝移植术中ALI的发生。观察有无ALI患者血清细胞因子和外周血多形核白细胞(PMN)TLR4的表达。接下来，将自体原位肝移植(OALT)大鼠分为假手术组和模型组。分析肺功能、TLR4表达及细胞因子水平。此外，在OALT前接受TLR4-siRNA治疗的大鼠中，评估了TLR4在OALT介导的ALI中的作用。ALI组中性粒细胞TLR4表达及血清肿瘤坏死因子-α和IL-β水平均高于非ALI组。有趣的是，OALT后8h，肺组织TLR4表达显著增加，并伴有肿瘤坏死因子-α和IL-β水平的升高，从而导致肺组织病理损伤和肺组织髓过氧化物酶含量增加。此外，TLR4基因敲除减少了OALT后肺组织细胞因子的释放，逆转了上述病理变化，提高了大鼠的存活率。总之，TLR4的过度表达可能通过刺激促炎细胞因子的过度产生，促进了原位肝移植后ALI的发展。
Acute lung injury (ALI) is a severe complication of orthotopic liver transplantation (OLT) with unclear underline mechanism. Toll-like receptor 4 (TLR4) has been identified as a key receptor mediating inflammation. We hypothesized that TLR4-mediated pulmonary inflammation may contribute to development of ALI during OLT. Patients with or without ALI were observed for serum cytokines and expression of TLR4 on peripheral blood polymorphonuclear leukocytes (PMNs). Next, rats which underwent orthotopic autologous liver transplantation (OALT) were divided into sham and model groups. Pulmonary function and the level of TLR4 expression and cytokines were analyzed. Furthermore, the role of TLR4 in OALT-mediated ALI was assessed in rats treated with TLR4-siRNA before OALT. The PMNs TLR4 expression and the serum TNF-α and IL-β level were higher in patients with ALI than those with non-ALI. Interestingly, lung TLR4 expression was significantly increased after 8 hours of OALT with increased levels of TNF-α and IL-β, which lead to lung pathological damage and an increase of lung myeloperoxidase content. Moreover, knockdown of TLR4 reduced lung cytokines release and reversed the above pathologic changes after OALT and finally improved rats' survival rate. In conclusion, TLR4 overexpression, potentially by stimulating proinflammatory cytokine overproduction, contributes to the development of ALI after OLT.