Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle, NE2 4HH, UK.
Intensive Care Med. 2010 Jun;36(6):956-62. doi: 10.1007/s00134-010-1823-7. Epub 2010 Mar 12.
Loss of mitochondrial DNA (mtDNA) has been described in whole blood samples from a small number of patients with sepsis, but the underlying mechanism and clinical implications of this observation are not clear. We have investigated the cellular basis of the mtDNA depletion in sepsis, and determined clinical correlates with mtDNA depletion.
Whole blood samples were obtained from 147 consecutive patients with severe sepsis admitted to a General Critical Care Unit in a University Hospital and 83 healthy controls. In a separate study of 13 patients with severe sepsis, blood was obtained for immediate cell sorting by flow cytometry. MtDNA content was determined in whole blood DNA by PCR methods, and subsequently in the 13 samples where white cell subtypes were separated.
The mtDNA content of peripheral blood in human subjects was lower in patients with sepsis than controls (P < 0.0001). By studying leukocyte subsets in a subgroup of 13 patients, we showed that this was largely due to an increase in the proportion of circulating neutrophils, which contained approximately 3-fold less mtDNA than mononuclear leukocytes. However, isolated monocytes (P = 0.041) and lymphocytes (P = 0.021) from septic patients showed clear evidence of mtDNA depletion, which correlated with the APACHE II score (P = 0.015).
In severe sepsis much of the apparent whole blood mtDNA depletion is due to a change in the differential leukocyte count. However mtDNA depletion in mononuclear cells occurs in patients with sepsis and correlates with disease severity.
已有少数脓毒症患者的全血样本中出现线粒体 DNA（mtDNA）缺失的描述，但这种观察结果的潜在机制和临床意义尚不清楚。我们研究了脓毒症中 mtDNA 耗竭的细胞基础，并确定了与 mtDNA 耗竭相关的临床指标。
从一家大学医院的普通重症监护病房中连续收治的 147 例严重脓毒症患者和 83 例健康对照者中采集全血样本。在一项对 13 例严重脓毒症患者的独立研究中，通过流式细胞术立即采集血液进行细胞分选。采用 PCR 方法测定全血 DNA 中的 mtDNA 含量，随后在 13 例分离出白细胞亚型的样本中进行测定。
与对照组相比，脓毒症患者外周血中的 mtDNA 含量较低（P<0.0001）。通过对 13 例患者的白细胞亚群进行研究，我们发现这主要是由于循环中性粒细胞比例增加所致，中性粒细胞中 mtDNA 含量约为单核细胞的 3 倍。然而，从脓毒症患者中分离出的单核细胞（P=0.041）和淋巴细胞（P=0.021）中明显存在 mtDNA 耗竭，这与急性生理学和慢性健康状况评分系统（APACHE II）评分相关（P=0.015）。
在严重脓毒症中，全血 mtDNA 耗竭的大部分原因是白细胞分类计数的变化。然而，单核细胞中的 mtDNA 耗竭在脓毒症患者中发生，与疾病严重程度相关。
