Effects of DDR2 siRNA on carbon tetrachloride-induced liver fibrosis in rats / 中华肝胆外科杂志

ABSTRACT

Objective To explore the effects of silencing DDR2 expression by siRNA on CCl4-induced liver fibrosis and its mechanism in rats. Methods Liver fibrosis model was induced by intraperitoneal injection of CCl4 twice a week for 6 consecutive weeks. Some rats were administered siRNA targeting DDR2 (0. 3 mg/kg), saline or control siRNA every three days from the beginning of CCl4 injection via tail vein injection, while other rats were treated in the same pattern after 2-week CCl4 injection. Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot were used to detect the mRNA and protein expressions of DDR2, MMP-2 and COL Ⅰ . Meanwhile, the pathological changes of liver tissues and the levels of liver function were also observed. Results QRT-PCR showed that the DDR2, MMP-2 and COL Ⅰ mRNA in the chemically synthetic cholesterol-modified siRNADDR2 group were significantly decreased as compared with those in the control group (P＜0.01) ,and the protein expressions of DDR2, MMP-2 and COL Ⅰ were also significantly decreased (P＜0. 01,4 wand 6w). In addition, in comparison with those in the control group, the pathological changes of liver tissues in the siRNA-DDR2 treated group were markedly attenuated, and the levels of ALT(1356.17 ±83.80 nkat/L vs 2532. 70±145.11 nkat/L,4w,1367. 60±321.76 nkat/L vs 2604.37±255.02 nkat/L,6w,P＜0. 01 ) and AST (2460. 80 ± 207. 58 nkat/L vs 3983. 70 ± 253. 08 nkat/L, 4w, P＜ 0. 01,2383.27±290.16 nkat/L vs 3227.70±353. 34 nkat/L,6w,P＜0. 05)were also significantly lowered,while the level of TBIL (7. 97 ± 1.60 μmol/L vs 3.80± 0.60 μmol/L, 4w, 10.40±1.61 μmol/L vs 6.10±0.79 μmol/L,6w,P＜0. 01)was markedly increased. Conclusion Systemic administration of cholesterol-modified siRNA targeting DDR2 could significantly suppress the expression of DDR2, decrease the contents of the extracellular matrix,and thus has a potential antifibrotic effect.