Effect and mechanism of gdolinium chloride on hepatic ischemia/reperfusion injury in Sprague Dawley rats

Abstract

Objective To analyze the effect and mechanism of gadolinium chloride on hepatic ischemia-reperfusion injury (HIRI) in Sprague Dawley (SD) rats. Methods Thirty six eight weeks special pathogen free SD rats, were included in the project. The body weight ranged from 200 to 250 g. Thirty six rats were randomly divided into sham operation group, model group and gadolinium chloride group with 12 rats/group. Model of ischemia-reperfusion injury was generated in the rats of model group; In the gadolinium chloride group, preoperative intraperitoneal injection of gadolinium chloride was performed before the model of HIRI was established; In the sham operation group, only the abdomen was opened and closed and the hilum was dissected. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the three groups. The relative expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 β (IL-1β) mRNA were detected by Q-PCR. Western blot was used to detect the expression of markers involved in the Toll like receptor 2/myeloid differentiation factor 88 (MyD88) signaling pathway. Immunohistochemistry staining was used to detect the expression of Fas and Fas ligands in hilar bile duct epithelial cells. Results ALT and AST were (55±8) U/L, (92±22) U/L in sham operation group, lower than those in model group (1 247±62) U/L, (1 117±60) U/L, respectively, and ALT and AST in gadolinium chloride group were (622±50) U/L and (552±41) U/L, lower than those in model group (all P<0.05). Compared with the sham operation group, the relative expression of TNF-α, IL-1 β, IL-6 mRNA in the model group was significantly higher (all P<0.05), but the expression of those markers were higher than gadolinium chloride group (all P<0.05). Gadolinium chloride down-regulated the expression of Toll like receptor 2/MyD88 signaling pathway in rat with liver ischemia-reperfusion. The percentage of Fas protein positive cells in model group was (40.2±3.8)%, and the percentage of Fas ligand positive cells was (36.9±2.9)%, which was higher than those in gadolinium chloride group (29.7±2.3)% and (23.6±2.1)% with statistically significant differences (all P<0.05). Conclusion Gadolinium chloride can reduce the injury of liver function and inhibit the expression of inflammatory factors in liver tissue of SD rats with hepatic ischemia-reperfusion, which may play a protective role by down regulating the expression of relative protein in Toll like receptor 2/MyD88 signaling pathway. Key words: Reperfusion injury; Gdolinium chloride; Liver; Toll-like receptor 2; Myeloid differentiation factor 88