脑出血患者的二甲基精氨酸：与结局、血肿扩大和水肿的关系。
Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema.
机构信息
Department of Neurology, Hannover Medical School, 30623, Hannover, Germany.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
出版信息
J Neuroinflammation. 2017 Dec 13;14(1):247. doi: 10.1186/s12974-017-1016-1.
BACKGROUND
Asymmetric dimethylarginine (ADMA)--the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury.
METHODS
Blood samples from 20 patients with acute ICH were taken at ≤ 24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0-2) outcome, and 11 patients unfavorable outcome (mRS 3-6). Patients' serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography-tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging.
RESULTS
Levels of ADMA--but not SDMA and L-arginine--were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA ≤ 24 h, p = 0.003; 3 days p = 0.005; 7 days p = 0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels ≤ 24 h (p = 0.048) and at 3 days (p = 0.028) with unfavorable outcome. ADMA ≤ 24 h was increased in patients with hematoma enlargement (p = 0.003), while SDMA ≤ 24 h was increased in patients with large hematoma (p = 0.029) and perihematomal edema volume (p = 0.023).
CONCLUSIONS
Our data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind.
背景
不对称二甲基精氨酸（ADMA）——最强的内源性一氧化氮合酶抑制剂，被认为是内皮功能障碍和氧化应激的介质。考虑到实验数据，ADMA 及其结构异构体对称二甲基精氨酸（SDMA）的水平可能在脑出血（ICH）后升高，并与临床结局和继发性脑损伤相关。
方法
20 例急性 ICH 患者于发病后≤24 小时及 3 天和 7 天采集血样。9 例患者预后良好（90 天时改良 Rankin 量表（mRS）0-2），11 例患者预后不良（mRS 3-6）。采用高效液相色谱-串联质谱法测定患者血清 ADMA、SDMA 和 L-精氨酸水平。并与 30 例无 ICH 的对照组进行比较。为了进一步分析，根据患者的预后、血肿和血肿周围水肿体积、血肿扩大的发生以及计算机断层扫描和连续磁共振成像测量的细胞毒性水肿对患者进行分组。
结果
与对照组相比，ICH 患者的 ADMA 水平升高（二项逻辑回归分析：ADMA≤24 小时，p=0.003；3 天，p=0.005；7 天，p=0.004）。如果根据患者的预后对患者进行分组，则预后不良的患者二甲基精氨酸升高。二项逻辑回归分析证实，SDMA 水平在 24 小时内（p=0.048）和 3 天内（p=0.028）与不良预后相关。ADMA 在血肿扩大的患者中升高（p=0.003），而 SDMA 在血肿较大的患者中升高（p=0.029）和血肿周围水肿体积较大的患者中升高（p=0.023）。
结论
我们的数据表明，二甲基精氨酸与 ICH 的预后有关。然而，需要进一步的研究来证实这种关系，并阐明其背后的机制。
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