The liver sinusoidal endothelial cell damage in rats caused by heatstroke

Abstract

This study was designed to explore whether liver sinusoidal endothelial cells (SECs) play a pathological role in liver injury of heatstroke (HS) in rats. An HS rat model was prepared in a pre-warmed incubator. Rats were randomized into four groups: HS-sham group (SHAM group), the 39°C group, the 42°C group, and the HS group. The serum concentrations of SEC injury biomarkers including hyaluronic acid (HA), von Willebrand factor (vWF), thrombomodulin (TM), were measured. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and endothelium-derived vasoactive substances including endothelin-1 (ET-1) and nitric oxide (NO) were determined using a commercially available kit. Hepatic tissues were obtained for histopathological examination, electron microscopy examination, immunohistochemistry, and reverse transcription polymerase chain reaction (PCR) analysis. Our study team found increased levels of plasma ALT/AST during the course of HS. We were also able to detect microcirculation changes and inflammatory injury of the liver (especially in the sinusoidal areas). In addition, markers of SEC injury were significantly elevated. Thrombosis-related markers including vWF and TF expression levels were significantly upregulated and TM levels downregulated. Furthermore, imbalance between ET-1 and NO levels were detected. In conclusion, damage of SECs could result in microcirculation disturbances and pro-inflammatory injury in the liver during HS, which could prove to be a potential pathogenic mechanism of liver injury in HS.