Regulation of hepatic micro circulation by hepatic stellate cell-Application of NAC to liver failure

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Hepatic stellate cell. is known to regulate hepatic sinusoidal blood flow through its contraction and relaxation. When it is contracted by activation, sinusoidal blood flow is reduced. Therefore, it is considered that regulation of activation of hepatic stellate cell can be a potential strategy to improve hepatic microcirculation. We have clarified in TAA-induced cirrhosis model of rats that N-acetyl-L-cysteine (NAC) has a powerful effect on prevention of hepatic stellate cell activation and progress of fibrosis. In such model, microcirculation was well maintained. Rock/Rho kinase inhibitor, Y-27632 is also known to prevent activation of hepatic stellate cell and prevent fibrosis. In this study, we have examined whether Y-27632 has an effect on improvement of hepatic microcirculation. We have investigated it in ischemia/reperfusion model of rat liver using hemi-lateral clamp of the liver. Y-27632 protected ischemia/reperfusion-induced injury of the liver through remarkable improvement of hepatic microcirculation, which was observed by intravital microscopy. Diamiter of sinusoid and postsinusoidal venule, sinusoidal :perfusion rate were maintained as compared to sham group. Adherence of leucocytes in the sinusoid and postsinusoidal venule was much less, which results also in protection of disturbance of the blood flow. Y-27632 also exhibited to improve disturbance of microcirculation due to endotoxemia. Tioredoxin has an effect of antioxidant like NAC. We clarified that thioredoxin prevents hepatic fibrosis in the chronic liver injury model and also protect hepatic cell death in acute hepatitis model.