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Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

World Journal of Gastroenterology 2012年第22期18卷 2798-2804页

作者： jeanine ward Shashi Bala Jan Petrasek Gyongyi Szabo Department of Emergency Medicine University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 United States Division of Gastroenterology Department of Medicine University of Massachusetts Medical School 364 Plantation Street Worcester MA 01655 United States

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

关键词： Plasma microRNA Hepatotoxicity Acet-aminophen Drug-induced liver injury Alanine amino-transferase

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