The effect of heme oxygenase-1 modified rat bone marrow mesenchymal stem cells on rats with liver fibrosis / 中华肝胆外科杂志

ABSTRACT

Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified rat bone marrow mesenchymal stem cells (BMSCs) on fibrotic rats.Methods:110 male SD rats aged 6-8 weeks were selected randomly divided into model group, BMSCs group and HO-1/BMSCs group with 11 rats in each group after intraperitoneal injection of CCl 4, PBS, BMSCs and HO-1/BMSCs were injected respectively. Another 11 rats were selected as control group. After 4 weeks of intervention, tracer experiment was used to detect the location of BMSCs. Rats in each group were executed, and liver function were detected by biochemical analyzer, liver fibrosis indexes were detected by ELISA, liver histopathology were detected by HE and Sirius red staining. Immunohistochemistry, Western blot and RT-PCR were used to detect the protein and mRNA expression of E-cadherin and Vimentin. Results:The rat fibrosis model was successfully established. Tracer experiment showed that BMSCs were implanted in rat liver after transplantation. Compared with the model group, the liver function and liver fibrosis indexes of BMSCs group and HO-1/BMSCs group were improved, and Ishak score and stage were significantly decreased, and HO-1/BMSCs group was superior to BMSCs group. The expression of E-cadherin in HO-1/BMSCs group (0.92±0.21), (0.84±0.03) were higher than those in BMSCs group [(0.54±0.16), (0.53±0.04)] and model group [(0.49±0.06), (0.11±0.06)] both at protein and mRNA level, while protein and mRNA level of Vimentin (1.21±0.23), (3.82±0.80) were lower than that in BMSCs group [(1.32±0.17), (6.39±0.75)] and model group [(1.41±0.18), (16.94±1.30)]. The difference was statistically significant ( P<0.05). Conclusion:HO-1/BMSCs can improve liver function and liver fibrosis in fibrotic rats more effectively than BMSCs alone. The mechanism was possibly through inhibiting liver epithelial mesenchymal transition.