Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis
J. Clin. Invest. Yaping Liu, et al. 112:1678 doi:10.1172/JCI18945 [
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Figure 5Protection against bile duct ligation–induced necrosis, mitosis, and bile duct proliferation by GW4064. Rats (
n = 6) were subjected to bile duct ligation or laparotomy without bile duct ligation (sham-operated). Beginning 24 hours after bile duct ligation surgery, the rats were treated for 4 days with vehicle, GW4064, or TUDCA. Livers were taken for histological analysis 4 hours after the final dose. The panels show representative H&E-stained liver sections from each treatment group at ×400 magnification. (
a) Sham-operated rats showing normal liver histology. (
b) Vehicle-treated BDL rat showing bile duct proliferation (open arrow) and parenchymal necrosis (filled arrow) with inflammatory cell infiltration. (
c) GW4064-treated BDL rat showing bile duct proliferation (white arrow) and fatty cell degeneration (shaded arrow). (
d) TUDCA-treated BDL rat showing parenchymal necrosis (filled arrow) with inflammatory cell infiltration. (
e) Mitotic nuclei were counted in samples from all rats. Mitosis was quantified by expressing the number of hepatocytes showing mitotic nuclei as a percentage of the total number of hepatocytes. White bars, sham; black bars, vehicle (Veh); dark gray bars, GW4064; light gray bars, TUDCA. Values are presented as average ± SEM. Statistically significant differences between the sham-operated and vehicle/BDL groups are indicated (
#P < 0.05). Statistically significant differences between the vehicle/BDL group and either the GW4064-treated or the TUDCA-treated groups are also indicated (*
P < 0.05). (
f) Bile duct proliferation was quantified by measuring the area occupied by cholangiocytes in 40–50 randomly selected fields under ×400 magnification. Groups as in
e; statistics as in
e.
