OBJECTIVETo design and synthesize small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) and to investigate its effect on liver fibrosis.

METHODSThe interference sequence of CTGF was designed and synthesized. Rat hepatic fibrosis model was induced by intraperitoneal injection of 40 % CCl4(3 ml/kg). Thirty male rats were randomly divided into 5 groups: in normal control and model groups rats received tail vein injection of normal saline every 3 days for 8 consecutive weeks; in preventive group rats received tail vein injection of CTGF siRNA (0.1 mg/kg) every 3 days for 8 weeks; in 2-w treatment group CTGF siRNA was given for 6 weeks starting from two weeks after CCl4 injection; in 4-w treatment group CTGF siRNA was given for 4 weeks starting 4 weeks after CCl4 injection. The serum and hepatic tissue samples were harvested 3 days after the last CCl4 injection. Hepatic fibrosis indices were measured. Expression of CTGF mRNA and protein in the liver was evaluated by RT-PCR and Western blot, respectively. Fibrosis in rat liver was analyzed by Masson staining.

RESULTSCompared with model group (0.544 0.019), the expression of CTGF mRNA and protein in liver of both preventive(0.105 ± 0.003) and 2-w treatment groups (0.190 ± 0.006) were markedly down-regulated (P<0.05). Inflammation, necrosis and fibrosis in hepatic tissue were significantly attenuated. In addition, the serum ration of liver fibrosis indices was greatly reduced(P<0.05). Compared with preventive and 2-w treatment groups, the expression of CTGF mRNA and protein in liver in 4 weeks of treatment group were up-regulated (P<0.05); inflammation, necrosis and fibrosis in hepatic tissue were relative increased; and the serum concentrations of liver fibrosis indices were relatively higher (P<0.05).

CONCLUSIONThe highly effective CTGF siRNA has been successfully synthesized, which can inhibit CTGF expression in liver, prevent hepatic fibrosis and its progress in rats.