| Objective To investigate the effects of anti-inflammatory and antioxidant of curcumin derivative (Curc-OEG) on CC14-induced hepatic fibrosis in rats.Methods All rats were given subcutaneous injection of CC14 and olive oil mixture 2ml/kg, twice a week for 10 weeks. After 4 weeks, rats were randomly divided into model group, curcumin and Curc-OEG treatment groups and normal rats were used as control group. Rats of control and model group were treated with normal saline by intravenous 0.2ml/d, curcumin group were administrated with curcumin 400 mg.kg.d-1 by gavage and Curc-OEG group were treated with Curc-OEG 100 mg.kg-1.d-1 by intravenous respectively. Every group had 30 rats. After 2,4 and 6 weeks treatment, the serum levels of ALT,AST,HA,LN,PCⅢ,Ⅳ-C were tested. HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis. The mRNA expression of cytokines of NF-kB, IL-1β, IL-6, TNF-α, COX-1, COX-2 and iNOS were observed with Real Time PCR. The protein expression of NF-kB, TNF-α and COX-2 were tested by Western blot. The levels of MOD, SOD and GSH in the liver of rats were quantified.Results1) The hepatoprotective effect of Curc-OEG on liver:after 2 weeks treatment, the levels of ALT/AST in normal, model, curcumin, Curc-OEG groups were:31.7±4.0 U/L/160.0±34.4U/L,278.0±17.4U/L/308.0±6 0.7U/L,174.0±101.6U/L/243.0±105.3U/L,89.0±17.3U/L/156.0±44.2U/L. After four weeks treatment, the levels of ALT/AST were:31.7±8.7U/ L/137.7±32.7U/L,383.0±75.6U/L/585.3±36.7U/L,406.3±204.7U/L/485.0± 246.5U/L,107.0±73.7U/L/202.7±56.0U/L. After six weeks treatment, the levels of ALT/ASTwere:29.0±5.6/135.7±9.6U/L,549.7±251.2U/L/669. 3±220.6U/L,341.3±56.5U/L/507.7±165.6U/L,141.7±31.8U/L/362.7±53.2U /L. Curc-OEG possessed more hepatoprotective effects than curcumin (P<0.05)2) Effect of Curc-OEG on the levels serum of HA, LN, PCIII and IV-C:after six weeks treatment, the level of HA, LN, PCIII in normal, model, curcumin and Curc-OEG groups were:92.7±19.0ug/L, 292.8±105.6μg/L,222.3±38.1μg/L,150.0±26.0μg/L;LN were:27.7±6.9ug/ L,48.8±7μg/L,30.6±5.3μg/L,28.2±4.8μg/L; PCIII were:27.7±2.7ug/L, 46.3±6.4μg/L,37.6±6.5μg/L,30.2±3.8μg/L. Curc-OEG could obviously reduce the levels of HA,LN and PCIII (P<0.05) and had no obviou s effect on IV-C.3) Effect of Curc-OEG on attenuating liver fibrosis:after four weeks treatment, liver pathology showed Curc-OEG could significantly alleviate steatosis, reduce inflammation and apparently suppress hepatic fibrogenesis. After six weeks treatment, rats of model group showed more and thicker extracellular matrix, but Curc-OEG could obviously alleviate the progress of liver fibrosis and cirrosis. With the Ishak score, model group mainly distributed in the F5-F6 level, curcumin group mainly in the F3-F5 level and Curc-OEG group mainly in the F1-F4 level.4) Effect of Curc-OEG on anti-inflammation:compared with curcumin, Curc-OEG down-regulated mRNA expression levels of IL-1β, IL-6, TNF-a, COX-2 and iNOS (P<0.05). But Curc-OEG had no obvious effect on NF-kB mRNA expression. After 2,4,6 weeks treatment, the mRNA expression of COX-2 in model groups up-regulated 7,259,35 fold changes respectively compared with normal groups, but Curc-OEG significantly down-regulated the mRNA expressions of COX2 by 2,23,2 fold changes respectively compared with model groups. Curc-OEG could obviously suppress COX-2 mRNA expression of liver tissue.5) Effect of Curc-OEG on the protein expression of NF-kB and TNF-a: from Western blot analysis, Curc-OEG group down-regulated protein expression levels of NF-kB, TNF-a compared with model group. And the protein expression of COX-2 in liver too low to be detected.6) Moreover, Curc-OEG increased the levels of GSH during the whole treatment. But Curc-OEG had no obvious effect on MDA and SOD.Conclusion Curc-OEG showed better anti-inflammatory, anti-oxidant and anti-fibrotic effects than these of curcumin, which provided us a new agent for treatment of liver fibrosis and cirrhosis. |
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