Cryptdin-2 predicts intestinal injury during heatstroke in mice

Intestinal injury-induced bacterial translocation and endotoxemia are important in the pathophysiological process of heatstroke. However, the underlying mechanism remains to be fully elucidated. Previous studies using 2D-gel electrophoresis found that defensin-related cryptdin-2 (Cry-2), an intestinal α-defensin, is upregulated in intestinal tissues during heatstroke in mice, and that treatment with ulinastatin, a multivalent enzyme inhibitor, reduced heat-induced acute lung injury. To investigate the association between Cry-2 and heat stress (HS)-induced intestinal injury and the probable protective role of ulinastatin, the present study examined the intestinal expression of Cry-2 via histopathologic analysis and reverse transcription-quantitative polymerase chain reaction analysis in mice with heatstroke. The heat-stressed mice were exposed to different core temperatures and cooling treatments, and intestinal pathological changes and Chiu scores were determined. Chemical markers of intestinal injury, serum and intestinal concentrations of diamine oxidase (DAO) and D-lactic acid (D-Lac), and serum and intestinal concentrations of Cry-2 were also determined. Correlations were analyzed using Spearman's correlation analysis. It was found that HS upregulated the expression of Cry-2, and the serum and intestinal concentrations of Cry-2 were correlated with the severity of HS-induced intestinal damage, indicated by pathology scores and concentrations of DAO and D-lac. Ulinastatin protected the intestines from HS-induced injury and downregulated the expression of Cry-2, which was also correlated with the extent of intestinal injury. Therefore, ulinastatin administration may be beneficial for patients with heatstroke, and Cry-2 may be a novel predictor of HS-induced intestinal injury.