Effect of bone marrow mesenchymal stem cells and artesunate on liver fibrosis

Abstract

Objective To study the effects of bone marrow mesenchymal stem cells(BMSCs) transplantation combined with artesunate(Art) on rat model of liver fibrosis.Methods 20 rats from 120 SD rats were selected randomly as normal control group.10 rats from those were executed and extracted marrow to culture BMSCs.The other 90 rats were injected intraperitoneally with CCl4 to make liver fibrosis rat models.10 rats from the 90 rats were selected randomly to ensure the liver fibrosis model was made successfully after 10 weeks.Then,the rest 80 rats were divided randomly into 4 groups:model group,Art treated group,BMSCs transplantation group and Art + BMSCs transplantation group.Fibrous degeneration of the hepatic tissue was detected by Masson stain.The mRNA expression of α-SMA,TGF-β1 in liver were detected by RT-PCR.The hydroxyproline(Hyp) level in liver was detected by enzyme digestion method.Serum TNF-αand TGF-β1 were detected by ELISA.Serum hepatic fibrosis parameters were detected by chemiluminescence and serum liver functional parameters were detected by biochemistry method.Results Liver functional parameters of Art + BMSCs transplantation group were better than those of the other groups.ALB in Art + BMSCs transplantation group was (29.13 ± 3.48) g/L,which was significantly higher than (26.31 ± 2.42) g/L in Art treated group (24.35 ±3.12)g/L in BMSCs transplantation group and (20.14 ±2.86) g/L in model group.There were significant differences among the 4 groups(q =6.27 ～ 19.01,all P ＜ 0.05).Liver fibrosis parameters of Art + BMSCs transplantation group were better than other groups.Hyp in Art + BMSCs transplantation group was (1.03 ±0.16) μg/L,which was significantly lower than (1.56 ± 0.19) μg/L in Art treated group,(1.45 ± 0.24) μg/L in the BMSCs transplantation group and (3.57 ±0.91) μg/L in the model group.There were significant differences among the 4 groups (q =20.47 ～ 27.70,all P ＜ 0.05).The expression of TGF-β1 mRNA of Art + BMSCs transplantation group was lower than other groups.The index of TGF-β1 mRNA expression in Art + BMSCs transplantation group was (20.16 ± 5.21),which was lower than (58.15 ±9.16) in Art treated group,(46.31 ±6.82) in the BMSCs transplantation group and (97.08 ± 14.23) in the model group.There were significant differences among the 4 groups (q =20.35 ～ 44.93,all P ＜ 0.05).Conclusion There're synergistic effects between Art and BMSCs in the treatment of liver fibrosis. Key words: Artesunate; Mesenchymal stem cell transplantation; Liver cirrhosis