Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis.
Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis.
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DOI：
10.1186/cc12742
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发表时间：
2013-05-27
期刊：
影响因子：
--
通讯作者：
Kim JM
中科院分区：
文献类型：
--
作者：
Jeong SJ;Han SH;Kim CO;Choi JY;Kim JM
严重脓毒症与不可接受的高死亡率相关。最近的研究显示，败血症患者血管内皮生长因子（VEGF）水平升高，VEGF是一种有效的血管生成和血管通透性因子。VEGF水平与脓毒症严重程度之间也存在相关性。在这里，我们研究了抗VEGF抗体（贝伐单抗，Bev）在脓毒症实验模型中的作用。使用人脐静脉内皮细胞（HUVEC）、小鼠盲肠结扎穿孔（CLP）和脓毒症的内毒素血症模型。用脂多糖（LPS）和/或Bev处理HUVEC，收获细胞因子mRNA水平，使用半定量逆转录聚合酶链反应测定。同时检测HUVECs培养上清中炎性细胞因子的水平。此外，评价了Bev对CLP和脓毒症内毒素血症模型中死亡率的影响。与单独LPS相比，Bev和LPS处理显著降低HUVECs中炎性细胞因子的表达和水平。在CLP和内毒素血症模型中，相对于单独CLP或LPS，给予0.1 mg/kg Bev的小鼠的存活益处明显（分别为P <0.001和P = 0.028），并且对于不同时间的Bev的作用，相对于单独CLP，在治疗后6 h的小鼠中的存活益处明显（P = 0.033）。此外，Bev还能抑制内毒素血症小鼠肺、脾和肾的血管渗漏（P <0.05）。抗VEGF抗体可能是一种有前途的治疗剂，因为它通过降低炎症反应和内皮通透性而对脓毒症的存活具有有益作用。
Severe sepsis is associated with an unacceptably high rate of mortality. Recent studies revealed elevated levels of vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, in patients with sepsis. There was also an association between VEGF levels and sepsis severity. Here we investigate the effects of an anti-VEGF antibody (Bevacizumab, Bev) in an experimental model of sepsis. Human umbilical vein endothelial cells (HUVECs), murine cecal ligation and puncture (CLP), and endotoxemia models of sepsis were used. HUVECs were treated with lipopolysaccharide (LPS) and/or Bev, harvested and cytokine mRNA levels determined using a semi-quantitative reverse transcription-polymerase chain reaction assay. The levels of inflammatory cytokine were also determined in HUVECs supernatants. In addition, the effects of Bev on mortality in the CLP and endotoxemia models of sepsis were evaluated. Treatment with Bev and LPS significantly decreased the expression and the level of inflammatory cytokines in HUVECs relative to LPS alone. In CLP and endotoxemia models, survival benefits were evident in mice given 0.1 mg/kg of Bev relative to the CLP or LPS alone (P <0.001 and P = 0.028, respectively), and in 6 h post-treated mice relative to the CLP alone for the effect of different time of Bev (P = 0.033). In addition, Bev treatment inhibited LPS-induced vascular leak in the lung, spleen and kidney in the murine endotoxemia model (P <0.05). Anti-VEGF antibody may be a promising therapeutic agent due to its beneficial effects on the survival of sepsis by decreasing inflammatory responses and endothelial permeability.
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影响因子：
4.8
作者：
Kim, I;Moon, SO;Koh, GY
通讯作者：
Koh, GY
影响因子：
158.5
作者：
Ranieri, V. Marco;Thompson, B. Taylor;Williams, Mark D.
通讯作者：
Williams, Mark D.
DOI：
10.1016/j.vascn.2007.08.002
发表时间：
2008-01-01
影响因子：
1.9
作者：
Cornacoff, Joel B.;Howk, Kreg;Martin, Pauline
通讯作者：
Martin, Pauline
DOI：
10.1165/ajrcmb.22.6.3779
发表时间：
2000-06-01
影响因子：
6.4
作者：
Kaner, RJ;Ladetto, JV;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
5.1
作者：
Nolan, A;Weiden, MD;Gold, JA
通讯作者：
Gold, JA