Small interfering RNA targeting connective tissue growth factor inhibits rat liver fibrosis in vivo

Objective To explore whether the intraperitoneal 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 Thirty male rats were randomly divided into five groups.Rats received intraperitoneally injection of 40% CCl 4(3 mL/ kg) together with tail vein injection of saline every three days for 8 consecutive weeks were served as model group;CCl4 together with tail vein delivery of siRNA(0.1 mg/ kg) as preventive group;CCl4 for 2 weeks followed by CCl4 and CTGF siRNA for more than 6 weeks as curative group;CCl4 for 4 weeks followed by CCl4 and CTGF siRNA for more than 4 weeks as advanced curative group and only tail vein injection of saline for 8 weeks as control group.Blood sample and hepatic tissue from rats were harvested 3 days after the last CCl4 injection.Serum transaminase,albumin,total bilirubin and hepatic fibrosis indices were measured.The levels of CTGF mRNA and protein in rats liver was evaluated by RT-PCR and Western blot respectively.Inflammation and fibrosis in rats liver were analyzed on tissues sections with HE staining.Results Compared with model group,the expression of CTGF mRNA and protein in liver of both preventive and curative groups were markedly down-regulated(P0.05).Inflammation,necrosis and fibrosis in hepatic tissue were significantly attenuated.In addition,the level of transaminases and liver fibrosis indices was greatly reduced.Compared with model group,the expression of CTGF mRNA and protein in liver in advanced curative group were down-regulated(P0.05).Inflammation,necrosis and fibrosis in hepatic tissue were reduced.The level of transaminases and liver fibrosis indices were reduced.Compared with preventive and curative groups,the expression of CTGF mRNA and protein in liver in advanced curative group were up-regulated(P0.05).Inflammation,necrosis and fibrosis in hepatic tissue was increased.The level of transminases liver fibrosis indices was dlevated.Conclusion Tail vein delivery of CTGF siRNA could significantly inhibit CTGF expression in rat s liver in vivo,and effectively prevent rat s hepatic fibrosis.The earlier siRNA targeting CTGF was injected,the more preventive effect it had on the progress of liver fibrosis,especially on liver fibrosis in advanced stage,suggesting its potential in anti-fibrosis role in liver.