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

 
Original Article
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Triptolide inhibits NF-κB activation and reduces injury of donor lung
induced by ischemia/reperfusion
 

Jing-kang HE1, Shu-dong YU1, Hong-Jun ZHU1, Jun-chao WU2, Zheng-hong QIN2,3

1Department of Cardiothoracic Surgery, the First Hospital Affiliated to Soochow University, Suzhou 215006, China; 2Department of Pharmacology and Laboratory of Aging and Nervous Diseases, School of Medicine, Soochow University, Suzhou 215123, China

 

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

 

3 Correspondence to Zheng-hong QIN.
Phn/Fax 86-512-6588-0406.
E-mail zhqin5@hotmail.com
Received 2007-05-18      Accepted 2007-07-02

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