The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage.

The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage.
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DOI:
10.3390/ijms242316922
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发表时间:
2023-11-29
影响因子:
5.6
通讯作者:
Galea, Ian
Galea, Ian
中科院分区:
生物学2区
文献类型:
--
作者:
Bandyopadhyay, Soham;Garland, Patrick;Gaastra, Ben;Zolnourian, Ardalan;Bulters, Diederik;Galea, Ian

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触珠蛋白是人体抵御蛛网膜下腔出血 (SAH) 后释放的细胞外血红蛋白毒性的第一道防线。我们研究了 SAH 后脑脊液 (CSF) 和血清中触珠蛋白的反应。对来自 19 名对照者和 92 名 SAH 患者的配对脑脊液和血清样本进行了如下测定:脑脊液血红蛋白和触珠蛋白的超高效液相色谱法、血清触珠蛋白和多重脑脊液细胞因子的免疫测定法以及白蛋白的比色法。脑脊液触珠蛋白明显缺乏:99% 的细胞外血红蛋白未结合。 CSF/血清白蛋白 (qAlb) 和触珠蛋白 (qHp) 的商用于计算 CSF 触珠蛋白指数 (qHp/qAlb)。与对照组相比,SAH 患者的脑脊液中的触珠蛋白指数显着降低,尤其是触珠蛋白-1 等位基因携带者。 SAH 后血清触珠蛋白水平升高,并与脑脊液细胞因子水平相关。触珠蛋白变量与 SAH 后的长期临床结果无关。我们的结论是:(1)SAH后发生鞘内触珠蛋白消耗,在触珠蛋白-1等位基因携带者中更是如此; (2) SAH后血清触珠蛋白上调,与肝脏对中枢炎症的急性期反应一致; (3) 脑脊液中的触珠蛋白非常低,任何变化都太小,不会影响长期结果,强调了治疗性触珠蛋白补充剂的潜力。
Haptoglobin is the body’s first line of defence against the toxicity of extracellular haemoglobin released following a subarachnoid haemorrhage (SAH). We investigated the haptoglobin response after SAH in cerebrospinal fluid (CSF) and serum. Paired CSF and serum samples from 19 controls and 92 SAH patients were assayed as follows: ultra-performance liquid chromatography for CSF haemoglobin and haptoglobin, immunoassay for serum haptoglobin and multiplexed CSF cytokines, and colorimetry for albumin. There was marked CSF haptoglobin deficiency: 99% of extracellular haemoglobin was unbound. The quotients for both CSF/serum albumin (qAlb) and haptoglobin (qHp) were used to compute the CSF haptoglobin index (qHp/qAlb). CSF from SAH patients had a significantly lower haptoglobin index compared to controls, especially in Haptoglobin-1 allele carriers. Serum haptoglobin levels increased after SAH and were correlated with CSF cytokine levels. Haptoglobin variables were not associated with long-term clinical outcomes post-SAH. We conclude that: (1) intrathecal haptoglobin consumption occurs after SAH, more so in haptoglobin-1 allele carriers; (2) serum haptoglobin is upregulated after SAH, in keeping with the liver acute phase response to central inflammation; (3) haptoglobin in the CSF is so low that any variation is too small for this to affect long-term outcomes, emphasising the potential for therapeutic haptoglobin supplementation.
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