The effects of hepatic steatosis on thromboxane A2 induced portal hypertension

Abstract

Introduction and aim: Thromboxane (TX) A₂ 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 TXA₂-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 TXA₂) in the perfusate were measured after in situ liver perfusion with Zymosan (150μg/ml, 40-46min) or U46619 (TXA₂ analog, 0.1μM/ml, 40-46min). 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, TXA₂ analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA₂ in fatty livers might be a potential therapy of severe steatosis.

Keywords: Células de Kupffer; Esteatohepatitis no alcohólica; Kupffer cells; Nonalcoholic steatohepatitis; Rat; Rata; Zymosan.