RESUMO
ObjectiveTo investigate the protective effects and mechanism of ursodeoxycholic acid (UDCA) on α-naphthylisothi (ANIT)-induced cholestatic liver injury in rats.MethodsA total of 48 Sprague-Dawley (SD) rats were selected.Fouty-two rats were gavaged with ANIT (100 mg/kg) to induce acute liver injury,six rats were sacrificed 24 hours after the liver injury and the rats left were evenly divided into control group which were gavaged with saline and UDCA group which were gavaged with UDCA (20 mg/kg).Six rats were sacrificed at 48 hours,72 hours and 96 hours after modeling.The six untreated rats were set as blank control group.Serum and liver tissues of all rats were kept after sacrificed.Serum levels of alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil) and total bile acid (TBA) were tested,interleukin-10 (IL-10),interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA).The expression of multidrug resistance associated protein2 (Mrp2) at mRNA level in liver tissue was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and the inflammatory reaction activity of liver tissues was inspected with Haematoidin-Eosin (HE)staining under microscope.ResultsAt 48 hours after liver injury modeling,serum TBil (143.80± 12.08) μmol/L vs.(178.50±15.19) μmol/L,TBA (13.15±3.81) μmol/L vs.(21.68±7.93)mol/L,IL-10 (44.13±3.68,37.15±6.25 ng/L),IL-6(50.80±2.09,57.32±4.63 ng/L) and TNF-α (17.53±0.84) ng/L vs,(19.10±1.64) ng/L of UDCA group and control group were compared,and the differences were statistically significant (P ＜ 0.01 or P＜ 0.05).At 72 hours after liver injury modeling,serum ALT (721.67±97.54) U/L vs.(929.50±148.29) U/L and IL-10 (54.68±6.79)ng/L vs.(43.85±4.08) ng/L of UDCA group and control group were compared,and the differences were statistically significant (P＜0.01 or P＜0.05).At 96 hours after liver injury modeling,serum ALT (156.83±14.99) U/L vs.(250.67±42.29) U/L,AST (143.67±27.45) U/L vs.(206.00±63.94) U/L and TBil (23.53±5.08) μmol/L vs.(34.02±9.98) μmol/L of UDCA group and control group were compared,and the differences were statistically significant (P＜0.01 or P＜0.05).The differences of Mrp2 expression at mRNA level in liver tissues between UDCA group and control group at 48 hours (0.77 ± 0.21,0.46 ± 0.25),72 hours (2.27 ±0.84,1.10 ±0.38) and 96 hours (3.64±0.54,2.75±0.69) after liver injury modeling were statistically significant (P＜0.01 or P＜0.05).ConclusionThe mechanism of the protective effects of UDCA on ANIT-induced liver injury may be related with the regulation of serum cytokines and liver Mrp2 expression.
