Objective: Major histocompatability complex class I chain-related antigen A, B (MICA, B) functions as ligands for human NKG2D receptors, which may play a role in graft rejection and cellular stress. In this study we explored the effect of ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B homologues) in mice to study the protective effect of Yisheng injection (YS), an herbal preparation developed from traditional Chinese medicine.
Methods: Male BALB/c mice were divided into sham, ischemic, and YS-treated groups using 90 minutes of left liver lobe ischemia. Sham control mice underwent the same operation, but without vascular occlusion. In the treated group, YS (20 mg/kg) was given before ischemia and after reperfusion for 7 days. Liver samples collected at 7 days postoperation were used for real-time quantitative polymerase chain reaction analysis, Western blotting, and immunohistochemical assays.
Results: Compared with the sham group, H60 and RAE-1 mRNA levels were increased by sevenfold and 4.5-fold in the ischemic group, respectively. After YS treatment, they were reduced by 76% and 70%, respectively. Western blotting and immunohistochemical assays showed that there was absent or faint H60 and RAE-1 expression in sham liver, but they were apparently increased in ischemic liver; however, the expressions were significantly decreased in the presence of YS.
Conclusions: Hepatic IRI significantly increased H60 and RAE-1 expression in mouse liver. YS treatment effectively reduced this increase, seeming to attenuate NKG2D-ligand-mediated immune responses caused by IRI. This may suggest a new concept to prevent IRI and graft rejection.