Dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis / 中华传染病杂志

ABSTRACT

Objective To explore the dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis. Methods A total of 42 healthy male SD rats were randomly divided into normal control group (n=6) and model group (n= 36). The model group was further divided into six subgroup according to different time points subgroups of 4 days, 1, 2, 4, 6 and 8 weeks with six rats in each subgroup. The rat model of hepatic fibrosis was induced by dimethylnitrosamine (DMN). The serum levels of alanine aminotransferase (ALT), aspertate aminotransferase (AST), albumin (Alb) and hyaluronic acid (HA) were detected dynamically after 4 days, 1,2,4,6 and 8 weeks of injection. The liver tissues were observed under optical microscope after HE and Masson staining. Notch-1, Jagged-1 mRNA and protein in liver were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The comparison of means among groups was done by univariate ANOVA. Results The hepatic fibrosis model was successfully induced by DMN injection and pseudolobules were found after 4 weeks of injection. The serum levels of ALT, AST, Alb and HA were all increased after 4 day of injection and peaked at week 4 which were all significantly higher than those in control group (F=83.10, 104.63, 54.24, 203.81,respectively; all P＜0.05). The expressions of Notch-1, Jagged-1 mRNA and protein in model group were all significantly increased than those in control group (F=282. 44, 369.14, 374.17, 256. 14,respectively;P＜0. 01). And the expressions of Notch-1, Jagged-1 were closely correlated with the hepatic fibrosis stages and transforming growth factor β1 (TGFβ1) expression (r=0. 821, 0. 917,0. 767,0. 844, respectively; P＜0. 01 ). Conclusions The Notch/Jagged pathway may participate in the development of hepatic fibrosis, which is closely correlated with the progression and severity of liver fibrosis.