Human umbilical cord mesenchymal stem cells improve liver damage of non-alcoholic fatty liver disease rats by down regulating HIF-1α/VEGF pathway

Abstract

Objective To evaluate the protective effect of human umbilical cord mesenchymal stem cells on non-alcoholic fatty liver disease and its relationship with HIF-1α/ VEGF mechanism in rats. Methods Rats were divided randomly into three groups: normal control (NC) , non-alcoholic fatty liver disease model (MC) and hUC-MSCs treatment group (MC+hUC- MSCs) . The number of each group was eight, the rats of each group were fed different diets and received 8 weeks' intervention. At the end of treatment, ALT, AST and HOMA-IR were measured respectively. The pathologyical changes of liver tissue were observed by light microscope. Then NAS was calculated. The expression of HIF-1α and VEGF protein in liver tissues were detected by Western Blot. Results (1) At the end of treatment, compared with the NC group, the values of ALT, AST and HOMA-IR in the MC group were significantly raised (P < 0.05) . MC, ALT, AST and HOMA- IR were significantly reduced in the MC+hUC-MSCs group. (2) By light microscope: The hepatocyte morphology was normal in NC group. The hepatocyte showed marked steatosis, more nuclear deformation, the lobules were misaligned with inflammatory cell infiltration in the MC group. The above liver histopathological changes were improved in the hUC-MSCs group. Compared with NC group, NAS was increased in the MC group, which could be reversed by hUC-MSCs[ (0.42 ± 0.23) vs (9.15±0.41) , (5.15±0.29) ]. (3) Compared with the NC group, the HIF-1α and VEGF protein expression by Western Blot in the liver tissues were significantly raised respectively. Compared with the MC group, the expressions indexes of HIF-1α and VEGF were reversed in the hUC-MSCs group (P < 0.05) . Single factor correlation analysis showed that HIF-1α protein level of of the liver tissues was dependent on HOMA-IR. Further, NAS score was dependent on HIF-1α and VEGF expression (r = 0.901、0.874, P < 0.05) . Conclusions Human umbilical cord mesenchymal stem cells can improve liver damage of non-alcoholic fatty liver disease rats. The effects may be related to down regulating HIF-1α /VEGF pathway. Key words: Non-alcoholic fatty liver disease; Human umbilical cord mesenchymal stem cells; HIF-1α; Vascular endothelial growth factor; Signal pathway