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异常快速上浮脱险诱导减压病模型中的代谢组学潜在血浆生物标志物及吡咯烷二硫代氨基甲酸盐的保护作用

Metabonomic potential plasma biomarkers in abnormal fast buoyancy ascent escape-induced decompression sickness model and the protective effects of pyrrolidine dithiocarbamic acid.

作者信息

Yiqun Fan, Pu You, Haitao Wang, Xiaochen Bao, Jun Ma, Shi Zhang, Yinghui Fan

机构信息

Department of Diving Medicine, Naval Medical Research Institute, Shanghai, 200433, People's Republic China.

Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic China.

出版信息

Undersea Hyperb Med. 2017 Mar-Apr;44(2):109-119. doi: 10.22462/3.4.2017.4.

Abstract

BACKGROUND

Decompression sickness (DCS) induced by fast buoyancy ascent escape (FBAE) is a special DCS, characterized with cardiopulmonary injuries. Serum metabonomics of this type of DCS has not yet been studied. We proposed a metabonomics approach for assessing serum metabonomics changes and evaluating the preventive effect of pyrrolidine dithiocarbamic acid (PDTC) in FBAE-induced DCS rats.

METHODS

Sixty-five (65) rats were divided into three groups, including the Control, DCS and PDTC groups. After receiving physiological saline or PDTC pretreatment, rats in the DCS and PDTC groups received the same protocol of simulated FBAE. Following this, a metabonomics approach - combined with pattern recognition methods including PCA and PLS-DA - was used to characterize the global serum metabolic profile on survival rats (five rats per group) associated with abnormal FBAE-induced DCS. As the VIP-value threshold cutoff of the metabolites was set to 2, metabolites above this threshold were filtered out as potential target biomarkers.

RESULTS

Sixteen (16) distinct potential biomarkers in rat plasma were identified. PDTC significantly lowered DSC mortality from 60% to 10%, and alleviated ultrastructural alteration of the left ventricular apex compared to the DCS group. It was found that abnormal FBAE-induced DCS was closely related to disturbed fatty acid metabolism, glycerophospholipid metabolism, sterol lipid metabolism, and bile acid metabolism. With the presented metabonomic method, we systematically analyzed the protective effects of PDTC.

CONCLUSION

The results demonstrated that PDTC administration could provide satisfactory effects on abnormal FBAE-induced DCS through partially regulating the perturbed metabolic pathways.

摘要

背景

快速浮力上升逃逸(FBAE)诱导的减压病(DCS)是一种特殊的DCS,其特征为心肺损伤。此类DCS的血清代谢组学尚未得到研究。我们提出一种代谢组学方法,用于评估血清代谢组学变化,并评价吡咯烷二硫代氨基甲酸(PDTC)对FBAE诱导的DCS大鼠的预防效果。

方法

65只大鼠分为三组,即对照组、DCS组和PDTC组。DCS组和PDTC组大鼠在接受生理盐水或PDTC预处理后,接受相同方案的模拟FBAE。之后,采用一种代谢组学方法——结合主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)等模式识别方法——对与FBAE诱导的异常DCS相关的存活大鼠(每组5只)的整体血清代谢谱进行表征。由于将代谢物的VIP值阈值设定为2,高于此阈值的代谢物被筛选出来作为潜在的靶标生物标志物。

结果

在大鼠血浆中鉴定出16种不同的潜在生物标志物。与DCS组相比,PDTC显著降低了DSC死亡率,从60%降至10%,并减轻了左心室心尖的超微结构改变。研究发现,FBAE诱导的异常DCS与脂肪酸代谢、甘油磷脂代谢、甾醇脂质代谢和胆汁酸代谢紊乱密切相关。利用所提出的代谢组学方法,我们系统地分析了PDTC的保护作用。

结论

结果表明,给予PDTC可通过部分调节紊乱的代谢途径,对FBAE诱导的异常DCS产生满意的效果。

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