Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCl(4) (2 mL/Kg, po) twice a week for 8 wk. Four weeks after CCl(4) treatment, thirty model rats were further divided randomly into 3 subgroups: CCl(4) and two
FMAC subgroups. Rats in CCl(4) and 2
FMAC subgroups were treated with
FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fifth week and the end of the eighth week. Spleen weight, blood synthetic markers (
albumin and prothrombin time) and hepatic
malondialdehyde (MDA) and
hydroxyproline (HP) concentrations were determined. Expression of
collagen I,
tissue inhibitor of metalloproteinases (TIMP)-1 and
transforming growth factor beta1 (TGF-beta1)
mRNA were detected by RT-PCR. Histochemical staining of Masson's trichrome was performed.
RESULTS: CCl(4) caused
liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased
plasma albumin level. Compared with CCl(4) subgroup,
FMAC subgroup (1 g/kg) significantly decreased the prothrombin time (36.7+/-7.2 and 25.1+/-10.2 in CCl(4) and
FMAC groups, respectively, P<0.05) and increased
plasma albumin concentration (22.7+/-1.0 and 30.7+/-2.5 in CCl(4) and
FMAC groups, respectively, P<0.05). Spleen weight was significantly lower in rats treated with CCl(4) and
FMAC (1 g/kg) compared to CCl(4) treated rats only (2.7+/-0.1 and 2.4+/-0.2 in CCl(4) and
FMAC groups, respectively, P<0.05). The amounts of hepatic MDA and HP in CCl(4)+FAMC (1 g/kg) subgroup were also lower than those in CCl(4) subgroup (MDA: 3.9+/-0.1 and 2.4+/-0.6 in CCl(4) and CCl(4)+
FMAC groups, respectively, P<0.01; HP: 1730.7+/-258.0 and 1311.5+/-238.8 in CCl(4) and CCl(4)+
FMAC groups, respectively, P<0.01). Histologic examinations showed that CCl(4)+
FMAC subgroups had thinner or less fibrotic septa than CCl(4) group. RT-PCR analysis indicated that
FMAC (1 g/kg) reduced
mRNA levels of
collagen I,
TIMP-1 and
TGF-beta1 (
collagen I: 5.63+/-2.08 and 1.78+/-0.48 in CCl(4) and CCl(4)+
FMAC groups, respectively, P<0.01; TIMP-1: 1.70+/-0.82 and 0.34+/-0.02 in CCl(4) and CCl(4)+
FMAC groups, respectively, P<0.01; TGF-beta1:38.03+/-11.9 and 4.26+/-2.17 in CCl(4) and CCl(4)+
FMAC groups, respectively, P<0.01) in the CCl(4)-treated liver.
CONCLUSION: