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Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver
Authors:Anders R. Knudsen  Kasper J. Andersen  Stephen Hamilton‐Dutoit  Jens R. Nyengaard  Frank V. Mortensen
Affiliation:1. Department of Surgical Gastroenterology L, Aarhus University Hospital, Aarhus, Denmark;2. Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark;3. Stereology & Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark
Abstract:Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design‐unbiased stereological methods. Forty‐seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one‐third of animals were subjected to ischaemic preconditioning and one‐third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time‐point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α‐2‐macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α‐2‐macroglobulin are correlated to the volume of liver necrosis.
Keywords:experimental animal study  hepatic necrosis  HPB surgery  ischaemia/reperfusion injuries  liver
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