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 anti-inflammatory, 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 α 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 α and interleukin-6, were reduced in the triptolide pretreatment groups (50 and 100 μg) 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.