Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis.
Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis.
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DOI：
10.1186/cc7710
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Ipaktchi K
中科院分区：
文献类型：
--
作者：
Flierl MA;Stahel PF;Rittirsch D;Huber-Lang M;Niederbichler AD;Hoesel LM;Touban BM;Morgan SJ;Smith WR;Ward PA;Ipaktchi K
继发于血脑屏障(BBB)破坏的败血症脑病是败血症的已知并发症。然而，其病理生理机制仍不清楚。本研究探讨补体C5a受体阻滞剂对实验性脓毒症血脑屏障损伤和垂体功能障碍的预防作用。采用标准化盲肠结扎和穿孔(CLP)模型，SD大鼠接受中和抗C5a抗体或免疫前免疫球蛋白(Ig)G作为安慰剂。假手术的动物作为内部对照。安慰剂治疗的脓毒症大鼠在24小时内表现出严重的血脑屏障功能障碍，并伴有垂体C5a受体和促炎细胞因子表达的显著上调，尽管生长激素的基因水平显著减弱。安慰剂治疗脓毒症大鼠的病理生理变化通过中和抗C5a抗体恢复到假手术组正常的血脑屏障和垂体功能水平。总的来说，C5a的中和极大地改善了与败血症脑病相关的病理生理变化，暗示了在脓毒症中药物抑制C5a的概念的进一步理论基础。
Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
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影响因子：
3.7
作者：
Flierl, Michael A.;Rittirsch, Daniel;Chen, Anthony J.;Nadeau, Brian A.;Day, Danielle E.;Sarma, J. Vidya;Huber-Lang, Markus S.;Ward, Peter A.
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3.3
作者：
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通讯作者：
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影响因子：
15.9
作者：
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4.8
作者：
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