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Zhang, Jiang; Schewe, Julia; Li, Hanwei; Makeschin, Marie-Christine; Mahajan, Ujjwal M.; Gerbes, Alexander L. und Steib, Christian J. (2019): The effects of hepatic steatosis on thromboxane A(2) induced portal hypertension. In: Gastroenterologia Y Hepatologia, Bd. 42, Nr. 9: S. 534-541

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Abstract

Introduction and aim: Thromboxane (TX)A(2) was identified as an important vasoconstrictor during Zymosan induced portal perfusion pressure (PP) increase. We aimed at investigating whether hepatic steatosis influences the extent of TXA(2)-induced portal hypertension. Materials and methods: Sprague-Dawley rats were randomly divided into control and steatosis (induced by the special diet) groups. PP and TXB2 (stable degradation product of TXA(2)) in the perfusate were measured after in situ liver perfusion with Zymosan (150 mu g/ml, 40-46 min) or U46619 (TXA(2) analog, 0.1 mu M/ml, 40-46 min). The number of Kupffer cell (KC) was measured by immunohistochemistry with CD163. Results: Zymosan induced more TXB2 production and a higher PP increase in control group than in steatosis group despite more CD163 positive KCs in fatty livers. PP and TXB2 efflux revealed a strong correlation in control group and a moderate correlation in steatosis group. Contrary to the effect of Zymosan, U46619 induced a much higher PP increase in steatosis group than in control group. Conclusion: Severe steatosis increased number of KCs, however, PP increase and TXB2 efflux caused by Zymosan infusion in fatty livers were lower than those in healthy livers. In contrast, TXA(2) analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA(2) in fatty livers might be a potential therapy of severe steatosis. (C) 2019 Elsevier Espana, S.L.U. All rights reserved.

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