Abstract
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.
Similar content being viewed by others
Article PDF
References
Peralta C, Fernández L, Panés J, Prats N, Sans M, Piqué JM, et al. Preconditioning protects against ischemia-reperfusion through blockade of tumor necrosis factor-induced P-selection up-regulation in the rat. Hepatology 2001; 33: 100–13.
Azzolina A, Bongiovanni A, Lampiasi N . Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochem Biophys Acta 2003; 1643: 75–83.
Jiang B, Xu S, Brecher P, Cohen RA . Growth factors enhance interleukin-1 beta-induced persistent activation of nuclear factor-kappa B in rat vascular smooth muscle cells. Aterioscler Thromb Vasc Biol 2002; 22: 1811–6.
Qin ZH, Wang YM, Nakai M, Chase TN . Nuclear factor-κB contributes to excitotoxin-induced apoptosis. Mol Pharmacol 1998; 53: 33–42.
Qin ZH, Chen RW, Wang YM, Nakai M, Chuang DM, Chase TN . NF-κB nuclear translocation up-regulates c-Myc and p53 during N-methyl-D-aspartate receptor-mediated apoptosis. J Neurosci 1999; 19: 4023–33.
Hu K, Liu Z, Liu D . Triptolide inhibits vascular endothelial growth factor expression and production by endothelial cells. Zhonghua Yixue Zazhi 2001; 81: 1106–9. Chinese.
Liu H, Liu ZH, Chen ZH, Yang JW, Li LS . Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol Sin 2000; 21: 782–6.
He JK, Gu ZL, Yu SD, Shen ZY . Triptolide on inhibition of reperfusion injury and prolongation of allograft survival in rat cardiac transplants. Chin J New Drugs Clin 2001; 20: 423–6. Chinese.
Luh SP, Tsai CC, Shau WY, Shiau SY, Jan JS, Kuo SH, et al. Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heartbeat donors. J Heart Lung Transplant 2002; 21: 251–9.
Rega FR, Wuyts WA, Vanaudenaerde BM, Jannis NC, Neyrinck AP, Verleden GM, et al. Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor. J Heart Lung Transplant 2005; 24: 1369–77.
Thabut G, Vinatier I, Stern JB, Leseche G, Loirat P, Fournier M, et al. Primary graft failure following lung transplantation. Predictive factors of mortality. Chest 2002; 121: 1876–82.
Hertz MI, Taylor DO, Trulock EP, Boucek MM, Mohacsi PJ, Edwards LB, et al. The registry of the international society for heart and lung transplantation: nineteenth official report — 2002. J Heart Lung Transplant 2002; 21: 950–70.
Perrot M, Liu M, Weddel K, Keshavjee S . Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2003; 167: 490–511.
Haydock DA, Trulock EP, Kaiser LR, Knight SR, Pasque MK, Cooper JD . Management of dysfunction in the transplanted lung: experience with 7 clinical cases. Washington University Lung Transplant Group. Ann Thorac Surg 1992; 53: 635–41.
Mathias MA, Tribble CG, Dietz JF, Nguyen RP, Shockey KS, Kern JA, et al. Aprotinin improves pulmonary function during reperfusion in an isolated lung model. Ann Thorac Surg 2000; 70: 1671–4.
Schmidt C, Peng B, Li Z, Sclabas GM, Fujioka S, Niu J . Mechanisms of pro-inflammatory cytokine-induced biophasic NF-κB activation. Mol Cell 2003; 12: 1287–300.
Gao ZG, Zang AC, Bai RX, Radix, Tripterygium wilfordii Hook F in rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis. Chin Med J 1986; 99: 317–20.
Jiang X . Clinical observations on the use of the Chinese herb Tripterygium wilfordii Hook for the treatment of nephrotic syndrome. Pediatr Nephrol 1994; 8: 343–4.
Wang J, Xu R, Jin R, Chen Z, Fidler JM . Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii. I. Prolongation of rat cardiac and renal allograft survival by the PG27 extract and immunosuppressive synergy in combination therapy with cyclosporine. Transplantation 2004; 70: 447–55.
Gu WZ, Chen R, Brandwein S, McAlpine J, Burres N . Isolation, purification, and characterization of immunosuppressive compounds from T ripterygium: triptolide and tripdiolide. Int J Immunopharmacol 1995; 17: 351–6.
Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin- 2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-κB transcriptional activation. J Biol Chem 1999; 274: 13 443–50.
Lu H, Hachida M, Enosawa S, Li X, Suzuki S, Koyanagi H . Immu-nosuppressive effect of triptolide in vitro. Transplant Proc 1999; 31: 2056–7.
Chan M, Kohlmeier JE, Branden M, Jung M, Benedict SH . Triptolide is more effective in preventing T cell proliferation and interferon-gamma production than is FK506. Phytother Res 1999; 13: 464–7.
He X, Verran D, Hu C, Wang C, Li L, Wang L, et al. Synergistic effect of Tripterygium wilfordii Hook F) (TWHF) and cyclosporin A in rat liver transplantation. Transplant Proc 2000; 32: 2054.
Fidler JM, Ku GY, Piazza D, Xu R, Jin R, Chen Z . Immunosup-pressive activity of the Chinese medicinal plant Tripterygium wilfordii III suppression of graft-versus-host disease in murine allogeneic bone marrow transplantation by the PG27 extract. Transplantation 2002; 74: 445–57.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
He, Jk., Yu, Sd., Zhu, HJ. et al. Triptolide inhibits NF-κB activation and reduces injury of donor lung induced by ischemia/reperfusion. Acta Pharmacol Sin 28, 1919–1923 (2007). https://doi.org/10.1111/j.1745-7254.2007.00701.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00701.x
Keywords
This article is cited by
-
Triptolide with hepatotoxicity and nephrotoxicity used in local delivery treatment of myocardial infarction by thermosensitive hydrogel
Journal of Nanobiotechnology (2023)
-
Renal-targeting triptolide-glucosamine conjugate exhibits lower toxicity and superior efficacy in attenuation of ischemia/reperfusion renal injury in rats
Acta Pharmacologica Sinica (2016)