Small interfering RNA targeting connective tissue growth factor prevents rats liver fibrosis

Objective To explore whether portal vein injection of small interfering RNA(siRNA) targeting connective tissue growth factor(CTGF) could inhibit CTGF expression in rats liver in vivo and prevent rats hepatic fibrosis. Methods Twenty four male rats were equaly divided into four groups. Rats received subcutaneous injection of 40% CCl4 (3 ml/kg) together with portal vein injection of saline every three days for 6 consecutive weeks were served as model group; CCl4 together with portal vein delivery of siRNA (0.1 mg/kg) as preventive group; CCl4 for 2 weeks followed by CCl4 and CTGF siRNA for more than 4 weeks as curative group, and only intraportal injection of saline as control group. Portal vein pressure in all rats at 3 days after the last CCl4 injection were measured, and blood and hepatic tissue from rats were harvested. Serum concentration of transaminases, hyaluronic acid(HA) and procollagen type Ⅲ (PⅢNP) were measured. Expression of CTGF mRNA and protein in rats liver was evaluated by RT-PCR and Western blot, respectively. Inflammation and fibrosis in rats liver was analyzed by H-E and Sirius red collagen staining. The fibrotic area was measured quantitatively by a computer-aided manipulator. Results Compared with model group, the expression of CTGF mRNA and protein in liver in both preventive and curative groups were markedly down-regulated. Inflammation, necrosis and fibrosis in hepatic tissue was significantly attenuated. In addition, the serum concentration of transaminases, HA and PⅢNP were greatly reduced. The fibrotic areas in preventive, curative and model groups were 5.8%±0.8%, 7.2%±0.9% and 12.3%±0.8%,respectively (P0.01), while the portal vein pressure were (14.2 ± 2.3 ), (15.1 ± 3.6 ) and ( 20.6 ± 5.8) cm H2O ,respectively (P0.01). Conclusions Portal vein delivery of CTGF siRNA significantly inhibit CTGF expression in rats liver in vivo, and effectively prevent rats hepatic fibrosis, suggesting siRNA targeting CTGF has the potential to be a novel strategy for anti-liver fibrosis.