International Journal of Medical Sciences

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14 December 2017

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Int J Med Sci 2015; 12(7):576-582. doi:10.7150/ijms.12111

Research Paper

Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest

Ya-Ping Zhang1, Yao-Bin Zhu1✉, Dayue Darrel Duan2, Xiang-Ming Fan1, Yan He1, Jun-Wu Su1, Ying-Long Liu1✉

1. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029
2. Laboratory of Cardiovascular Phenomics, the Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA 89557

Abstract

Background: Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.

Methods: Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.

Results: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.

Conclusion: Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

Keywords: ubiquitin C-terminal hydrolase-L1, neuronal apoptosis, deep hypothermic circulatory arrest, cardiopulmonary bypass

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How to cite this article:
Zhang YP, Zhu YB, Duan DD, Fan XM, He Y, Su JW, Liu YL. Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest. Int J Med Sci 2015; 12(7):576-582. doi:10.7150/ijms.12111. Available from http://www.medsci.org/v12p0576.htm