Abstract: Objective This experiment aimed at exploring the role of E series of prostaglandin receptor 4 (EP4) on liver fibrosis-related protein expression in mice with CCL₄-induced liver injuries. Methods 30 C57BL/6N mice were randomly divided into control, CCL₄-intervened, and CCL₄ and E7046 conbination-intervened group, with 10 mice in each group. The liver injury model was established by CCL₄ intraperitoneal injection, with methylcellulose or EP4-specific antagonist, E7046 solution gavage. After 27 day experiment, the mice were sacrificed under anesthesia, and sera and liver tissues were obtained. The EP4 and α-SMA protein expression and their mRNA levels were detected by Western blot and real-time PCR. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured by automatic biochemical instrument. The liver histopathological examination was performed by HE, Masson and Sirius red staining. Results The hepatic expression of EP4 protein in model mice increased greatly compared to in the control, while it decreased obviously in the combination-intervened mice compared to in the model; similarly, the EP4 encoded Ptger 4 mRNA level in the model group was (3.5±0.1), significantly higher than [(1.0±0.1), P<0.05] in the control, while that was (2.4±0.2) in the combination group, significantly decreased compared to in the model(P<0.05); serum ALT and AST levels in the model were (1753.5±328.6)U/L and (1586.2±204.1)U/L, much higher than in the control(P<0.05), while they decreased greatly in CCL₄ and E7046 combination group, e.g., [(885.9±269.6)U/L and (892.4±208.6)U/L, respectively, P<0.05]; the hepatic α-SMA expression in the model was stronger than in the control, while it became obviously weaker in CCL₄ and E7046 combination group, and the hepatic Acta2 and Col1a1 mRNA levels in the model up-regulated greatly compared to in the control, and also they became decreased in the CCL₄ and E7046-intervened group (P<0.05). Conclusion EP4 might play an pivotal role in CCL₄-induced liver fibrosis, which seem to be a target for ameliorating liver fibrosis.

Key words: Liver fibrosis, Carbon tetrachloride, E-type prostaglandin receptor 4, Ptger 4 gene, Mice