Objective: To investigate the mechanism of ursodeoxycholic acid (UDCA) in hepatocyte apoptosis using differentiated hepatocytes derived from bone marrow mesenchymal cells.
Methods: Rat bone marrow mesenchymal cell was induced into mature hepatocytes in vitro and then treated with PBS (Cont), deoxycholic acid (DCA), DCA plus UDCA (U + D) or UDCA alone (UDCA). Cell apoptosis was detected by Hoechst staining and Caspase-3 activity measurement. The mRNA expressions of p53 and Bax were measured by semi-quantitative RT-PCR and real-time RT-PCR. The Bax protein expression was detected by immunohistochemistry.
Results: In comparison with Cont, DCA obviously induced hepatocyte apoptosis as measured by an increased cell count and a higher Caspase-3 activity (P < 0.05). These increments could be inhibited by addition of UDCA. The expressions of p53 and Bax in hepatocytes were up-regulated by DCA. These up-expressions could also be inhibited by UDCA. The DCA-induced increased count of Bax-positive cells could be reduced by UDCA.
Conclusion: UDCA inhibits DCA-induced hepatocyte apoptosis by down-regulating the expression of p53/Bax signal molecule.
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