Background

Objective

The cerebral ischemia/reperfusion greatly influences brain metabolism. Remote ischemia preconditioning (RIPC) is reported to confer neuroprotective effects against cerebral ischemia in animal models and human. This study aims to investigate the metabolomic profiles of cerebrospinal fluid (CSF) in patients treated with repetitive lower limb RIPC and provides an insight into possible mechanism underlying RIPC-induced neuroprotection.

Method

Fifty healthy patients undergoing minor surgery under spinal anesthesia were randomly allocated to 2 groups: control group (Group C, n = 25) and RIPC treatment group (Group T,n = 25). Repetitive limb RIPC were performed 3 sessions, consisting of three 5-min cycles per session from the day before surgery to the morning on the surgery day. The CSF samples were collected from 48 patients before intrathecal injection of local anesthetic. A proton nuclear magnetic resonance (¹H NMR)-based metabonomics approach was used to obtain the CSF metabolic profiles of the samples (n = 24 each). The acquired data were processed with MestReNova and followed by statistical analysis with SIMCA-P.

Results

The model obtained with the orthogonal partial least-squares discriminant analysis (OPLS-DA) identified difference of metabolite profiles between two groups. The validation of the discriminant analysis showed that the accuracy of the OPLS-DA model was 81.3%. Sixteen metabolites including glucose, amino-acids and organic acids et al. were identified as the most influential CSF biomarkers for the discrimination between two groups, which are involved in pathways of energy metabolism and amino-acids metabolism.

Conclusion

¹H NMR spectra combined with pattern recognition analysis offers a new and promising platform to investigate metabolic signatures in patients treated with RIPC. Our results suggest repetitive RIPC mainly changes energy metabolism and amino-acid metabolism in brain, which provides a potential mechanistic understanding of RIPC-induced tolerance to cerebral ischemia.

中文翻译：

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反复下肢远程缺血预处理后脑脊液的¹ H NMR代谢特征

背景

客观的

脑缺血/再灌注极大地影响脑代谢。据报道，远程缺血预处理（RIPC）可在动物模型和人类中赋予针对脑缺血的神经保护作用。这项研究旨在调查接受重复性下肢RIPC治疗的患者脑脊液（CSF）的代谢组学特征，并为了解RIPC诱导的神经保护作用的潜在机制提供见解。

方法

将五十名接受脊椎麻醉小手术的健康患者随机分为2组：对照组（C组，n = 25）和RIPC治疗组（T组，n = 25）。重复肢体RIPC进行了3次治疗，从术前一天到手术当天的早晨，每个疗程进行3个5分钟的循环。在鞘内注射局部麻醉剂之前，从48例患者中收集了CSF样品。基于质子核磁共振（¹ H NMR）的代谢组学方法用于获得样品的CSF代谢谱（每个n = 24）。使用MestReNova处理获取的数据，然后使用SIMCA-P进行统计分析。

结果

通过正交偏最小二乘判别分析（OPLS-DA）获得的模型确定了两组之间代谢物谱的差异。判别分析的验证表明，OPLS-DA模型的准确性为81.3％。16种代谢物，包括葡萄糖，氨基酸和有机酸等。被认为是区分两组的最有影响力的CSF生物标志物，它们参与了能量代谢和氨基酸代谢的途径。

结论

¹ H NMR光谱与模式识别分析相结合，为研究RIPC治疗的患者的代谢特征提供了一个新的有前途的平台。我们的研究结果表明，重复性RIPC主要改变大脑中的能量代谢和氨基酸代谢，这为RIPC诱导的对脑缺血的耐受性提供了潜在的机制理解。