Triptolide Attenuates Acute Small-for-Size Liver Graft Injury in Rats by Inhibition of Toll-like Receptor 4

Introduction. The mechanism underlying small-for-size graft failure after reperfusion is still unknown. Toll-like receptor 4 (TLR4) has attracted a great deal of attention in inflammation and allograft rejection in recent years. Medicinally, triptolide has antiinflammatory, immunosuppressive, and antineoplastic activities. In the present study, we studied the effect of triptolide on TLR4 expression in small-for-size grafts. Materials and Methods. The potential inhibitory effect of triptolide on TLR4 messenger ribonucleic acid and protein in a mouse model of small-for-size liver graft injury was assessed. We also assessed the expression of tumor necrosis factor alpha and interleukin-6 in this model. Results. The expression of hepatic TLR4 messenger ribonucleic acid and protein and downstream mediators, such as tumor necrosis factor a and interleukin-6, were reduced in the triptolide pretreatment groups (50 and 100 mu g) in small-for-size liver grafts. In these same triptolide pretreatment groups, edema and necrosis were reduced and the levels of alanine aminotransferase and aspartate aminotransferase were significantly decreased in these small-for-size liver grafts. Conclusions. This study showed that triptolide might inhibit TLR4 in vivo and that pretreatment with triptolide could inhibit TLR4 activation and reduce small-for-size liver graft injury.