Localization of Tissue Plasminogen Activator on Experimental Thrombi in Rats
スポンサーリンク
概要
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The localization of tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) on thrombi was investigated in disseminated intravascular coagulation rats (DIC rats) induced by thrombin. One hour after the intravenous infusion of thrombin to rats, the plasma fibrinogen level decreased, while the plasminogen activator activity in the plasma euglobulin fraction increased. The whole body autoradiography was studied after an injection of [^<125>I] fibrinogen in DIC rats. The high radioactivity which indicated the presence of microthrombi was observed in the renal cortex, liver, spleen and lung. Futhermore, a large venous thrombus with higher radioactivity was observed in the abdominal vena cava. These results show that the thrombin-treated animal is one of the best DIC models. After the intravenous administration of [^<125>I] t-PA, the autoradiograms of DIC rats showed a radioactivity in the blood and much higher radioactivities in the renal cortex, spleen and lung in comparison with the normal rat. However, there was no difference in the distribution of [^<125>I] u-PA between normal and DIC rats at all. The strong radioactivity of [^<125>I] t-PA but not [^<125>I] u-PA was observed on the surface of large thrombus in the vena cava. These results suggest that t-PA localizes more preferentially on microthrombi than u-PA. The ratio of the radioactivity in the tissue to that in the blood was calculated to compare quantitatively the localization of [^<125>I] t-PA and [^<125>I] u-PA on microthrombi formed in organs. The ratios of the [^<125>I] t-PA radioactivities in the kidney, lung and liver showed 1.6 to 2.5 times higher amounts in DIC rats as compared with normal rats. On the other hand, the ratios of the [^<125>I] u-PA radioactivities did not show a significant difference between normal and DIC rats. These results further support the preferential localization of t-PA on microthrombi formed in organs.
- 公益社団法人日本薬学会の論文
著者
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Kondo S
Nippon Hoechst Marion Roussel Ltd.
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Koide T
Faculty Of Pharmaceutical Sciences Osaka University
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Koide Takashi
Tokyo Research Laboratories Kowa Co. Ltd.
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KANDA Hiroyasu
日産化学工業株式会社中央研究所
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KIMATA Hideki
興和株式会社東京研究所
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Kimata H
Kowa Company Ltd. Tokyo
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KIMATA Hideki
Tokyo Research Laboratories, Kowa Co., Ltd.
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NAKAJIMA Katsuaki
Tokyo Research Laboratories, Kowa Co., Ltd.
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YAMAMOTO Susumu
Tokyo Research Laboratories, Kowa Co., Ltd.
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KONDO Syuhei
Tokyo Research Laboratories, Kowa Co., Ltd.
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Yamamoto S
Kagoshima Univ. Kagoshima Jpn
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Nakajima K
Tokyo Research Laboratories Kowa Co. Ltd.:asahi Chemical Industry Co. Ltd.
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Nakajima Katsuaki
Tokyo Research Laboratories Kowa Company Ltd.
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Koshi T
Tokyo Research Laboratories Kowa Co. Ltd.
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Yamamoto Susumu
Tokyo Research Laboratories Kowa Company Ltd.
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Kimata Hideki
Tokyo Research Laboratories, Kowa Co. Ltd.
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