The role of Fas mutation on non-alcoholic steatohepatitis in mice / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>Our previous study indicated that the death receptor Fas played a key role on hepatocyte apoptosis in nutritional steatohepatitis in mice. This study aimed to explore whether Fas mutation accelerated hepatic steatosis and inflammatory infiltration in methionine-choline deficient (MCD) diet feeding mice.</p><p><b>METHODS</b>Mice homozygous for the lymphoproliferation spontaneous mutation (C57BL/6J-Faslpr) and wild type C57BL/6J mice were fed with MCD diet for three weeks to induce non-alcoholic steatohepatitis (NASH). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and total cholesterol (TC) levels were detected by an Olympus AU5400 automatic chemical analyzer. The role of Fas gene mutation on NASH was assessed by comparing the severity of hepatic steatosis and inflammation in the liver sections, the mRNA and protein expressions of hepatic inflammatory and fibrogenesis related factors, proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGFb1).</p><p><b>RESULTS</b>The serum ALT levels of the wild type and Faslpr mice fed with MCD were significant higher than that of the control mice (126.33+/-10.50 U/L vs (25.00+/-10.14) U/L, (160.33+/-48.29) U/L vs (18.33+/-9.08) U/L, with the LSD-t value 12.02, 5.08 respectively, the P value<0.001, 0.007 respectively. The serum ALT levels showed no significant difference between the Faslpr and wild type mice fed with MCD, with the LSD-t value 1.19, the P value 0.229. The serum AST, TG and TC levels showed neithere significant difference among the four groups. MCD diet induced hepatic steatosis and inflammatory infiltration in both of the wild type and Faslpr mice. Especially, severer hepatic injury was observed in Faslpr mice as compared with wild type mice. The mRNA expression levels of cell proliferation factor PCNA and fibrogenesis growth factor TGF b1 in wild type mice fed with MCD were significantly higher than that of the control mice (2.84+/-0.73, 2.77+/-0.54 vs 1.31+/-0.18, 0.89+/-0.18), with the LSD-t value 4.99, 8.08 respectively, the P value 0.001, <0.001 respectively. The mRNA expression levels of PCNA and TGFb1 in Faslpr mice fed with MCD were significantly higher than that of the Faslpr control mice and the wild type mice fed with MCD (5.57+/-1.13, 5.73+/-0.89 vs 1.04+/-0.16, 0.85+/-0.11 and 2.84+/-0.73, 2.77+/-0.54), with the LSD-t value 10.15, 13.19 and 5.33, 6.91 respectively, the P value<0.001. The protein expressions levels of PCNA and TGFb1 were concordant with the mRNA.</p><p><b>CONCLUSIONS</b>Faslpr promoted hepatic steatosis and inflammatory infiltration in mice fed with MCD diet, which might associated with excessive release of cell proliferative, inflammatory and fibrogenesis factors.</p>