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Antisense oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury
Kenji Nakamura1, Yayoi Kadotani, Hidetaka Ushigome
1Department of Organ Transplant and Endocrine Surgery, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine, 465 Hirokoji, Kawaramachi, Kamigyo-ku, Kyoto City, Kyoto 602-8566, Japan. 2lion@mua.biglobe.ne.jp
Abstract:
Tissue factor (TF) is an initiation factor for blood coagulation and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury. AS-1/TF was delivered intravenously to Lewis rats. After 10 h, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 min and harvested. TF expression was studied using immunohistochemical staining. One of 10 rats survived in a 5-day survival rate and TF was strongly stained on endothelial cells in non-treatment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells. These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver.