Acta Pharmacologica Sinica 2007 December; 28 (12): 1919-1923; doi: 10.1111/j.1745-7254.2007.00701.x

Aim: To investigate the protective effect of triptolide (TRI) on ischemia/reperfusion-induced injury of transplanted rabbit lungs and to investigate the mechanisms underlying the actions of TRI.

Methods: We established the rabbit lung transplantation model and studied lung injury induced by ischemia/reperfusion and the inhibitory effect of TRI on NF-κB. The severity of lung injury was determined by a gradual decline in PvO₂, the degree of lung edema, the increase in the myeloperoxidase (MPO) activity, and the ultrastructural changes of transplanted lungs. The activation of NF-κB was measured by immunohistochemistry. The increase in intercellular adhesion molecule-1 (ICAM-1), which is the target gene of NF-κB, was evaluated by ELISA.

Results: After reperfusion, there was a gradual decline in the PvO₂ level in the control group (group I). The level of PvO₂ in the group treated with lipopolysaccharide (group II) was significantly decreased, whereas that of the group treated with TRI (group III) was markedly improved (P<0.01). In group III, the activity of MPO was downregulated, and the pulmonary edema did not become severe and the ultrastructure of the donor lung remained normal. The activity of NF-κB and the expression of ICAM-1 was significantly increased in the donor lungs. TRI blocked NF-κB activation and ICAM-1 expression.

Conclusion: The effects of TRI on reducing injury to donor lungs induced by ischemia/reperfusion may possibly be mediated by inhibiting the activity of NF-κB and the expression of the NF-κB target gene ICAM-1. Thus, TRI could be used in lung transplantations for improving the function of donor lungs.

Keywords: lung transplantation; ischemia/reperfusion injury; triptolide; NF-κB; inter-cellular adhesion molecule-1