Sustained Repression and Translocation of NTCP and Expression of MRP4 for Cholestasis after Rat 90% Partial Hepatectomy

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Background/Aims: To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model. Methods: Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested on 0, 1, 3, and 7 days for microarray analysis, the quantitative real-time polymerase chain reaction （RT-PCR）, Western blotting and immunohistochemistry to examine the expression of multidrug resistance protein 4 （Mrp4）, bile salt export pump（ Bsep） and sodium-dependent taurocholate cotransporting polypeptide（ Ntcp）. Results: Persistently elevated serum bile acids were observed on days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased on day 3. Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. Bsep, an export pump localized to the canalicular membrane, was unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, Ntcp was localized in the cytoplasm on days 3 and 7 and was hardly detected in the basolateral membrane. Conclusions: These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seemed to be responsible for the high blood bile acids levels after massive hepatectomy.

弘前医学. 64(Suppl.), 2013, p.S99-S106

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  • 弘前医学

    弘前医学 64 (Supplement), S99-S106, 2013-04-02

    弘前大学大学院医学研究科・弘前医学会

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