Small interfering RNA targeting connective tissue growth factor prevents rats liver fibrosis
- VernacularTitle:抗结缔组织生长因子小分子干扰RNA防治大鼠肝纤维化研究
- Author:
Guangming LI
;
Qing XIE
;
Yi SHI
- Publication Type:Journal Article
- Keywords:
Connective tissue growth factor;
Small interferon RNA;
Liver fibrosis
- From:
Chinese Journal of Digestion
1998;0(06):-
- CountryChina
- Language:Chinese
-
Abstract:
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% CCl4 (3 ml/kg) together with portal vein injection of saline every three days for 6 consecutive weeks were served as model group; CCl4 together with portal vein delivery of siRNA (0.1 mg/kg) as preventive group; CCl4 for 2 weeks followed by CCl4 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 CCl4 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 (P