Triptolide inhibits NF-kappaB activation and reduces injury of donor lung induced by ischemia/reperfusion.
OBJECTIVE
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-kappaB. 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-kappaB was measured by immunohistochemistry. The increase in intercellular adhesion molecule-1 (ICAM-1), which is the target gene of NF-kappaB, 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-kappaB and the expression of ICAM-1 was significantly increased in the donor lungs. TRI blocked NF-kappaB activation and ICAM-1 expression.


CONCLUSIONS
The effects of TRI on reducing injury to donor lungs induced by ischemia/reperfusion may possibly be mediated by inhibiting the activity of NF-kappaB and the expression of the NF-kappaB target gene ICAM-1. Thus, TRI could be used in lung transplantations for improving the function of donor lungs.
He
Jing-kang
JK
Department of Cardiothoracic Surgery, First Hospital Affiliated to Soochow University, Suzhou 215006, China.
Yu
Shu-dong
SD
Zhu
Hong-jun
HJ
Wu
Jun-chao
JC
Qin
Zheng-hong
ZH
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004852:Epoxy Compounds / Q000494:pharmacology; D008168:Lung / Q000648:ultrastructure; D016040:Lung Transplantation; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide