Effect of compound rhodiola sachalinensis A Bor on CCI4-induced liver fibrosis in rats and its probable molecular mechanisms

AIM: To explore the anti-fibrotic effect of a traditional Chinese medicine, compound rhodiola sachalinensis A Bor on CCl4-induced liver fibrosis in rats and its probable molecular mechanisms. METHODS: Ninety healthy male SD rats were randomly divided into three groups: normal group (n=-10), treatment group of compound rhodiola sachalinensis A Bor (n=-40) and CCl4-induced model group (n=40). The liver fibrosis was induced by CCl4 subcutaneous injection. Treatment group was administered with compound rhodiola sachalinensis A Bor (0.5 g/kg) once a day at the same time. Then the activities of several serum fibrosis-associated enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), N-acetyl-beta-D-glucosaminidase (β-NAG) and the levels ofserum procollagen Ⅲ (PCⅢ), collagen Ⅳ (CⅣ), hyaluronic acid （HA） were assayed. The histooathol(mical chanaes were observed with HE, VG and Masson stain. The expression of TGF-β1 mRNA,αl (I) mRNA and Na+/Ca2+ exchanger (NCX ) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in situ.RESULTS: Compound rhodiola sachalinensis A Bor significantly reduced serum activities of ALT, AST, β-NAG and decreased the levels of PCⅢ, CⅣ, HA, improved the liver histopathological changes, inhibited the expression of TGF-β1 mRNA, α(1) mRNA and Na+/Ca2+ exchanger mRNA in rats. CONCLUSION: Compound rhodiola sachalinensis A Bor can intervene in CCI4-induced liver fibrosis in rats, in which potential mechanisms may be decreasing the production of TGF-β1, reducing the production of collagen, preventing the activation of hepatic stellate cell (HSC) and inhibiting theexpression of TGF-β1 mRNA, αl(I) mRNA and Na+/Ca2+ exchanger mRNA.

Effective inhibition of expression of hepatitis B virus genes by DNAzymes

AIM: To evaluate the inhibitory effects of DNAzymes on the expressions of hepatitis B virus (HBV) s (HBsAg) and e (HBeAg) in 2.2.15 cells, and to explore the potential therapeutic effects of DNAzymes on replication of HBV genome. METHODS: DNAzymes DrzBS and DrzBC specific to HBV (aywsubtype) s gene ORF A^157UG and e gene ORF A^1816UG, were designed and synthesized. Inhibitory effects of DrzBS or DrzBC on the expressions of HBV s and e genes as well as HBV DNA levels in culture supernatants were observed in 2.2.15 cells. RESULTS: After being treated with DrzBS or DrzBC, the expression of HBV s or e genes in 2.2.15 cells was depressed dramatically. The maximum inhibition rate was 94.2% and 91.8% for DrzBS and DrzBC, respectively. The concentration for effective inhibition of both DrzBS and DrzBC was within 0.1-2.5 μmol/L, showing a dosedependence. The efficiency of inhibiting HBsAg, HBeAg in 2.2.15 cells by DrzBS or DrzBC was higher than that of the same target genes by antisense oligonucleotides (ASON). The concentration for effective inhibition of DNAzymes was at least 10-fold lower compared with ASON controls. Neither inhibition on the replication of HBV DNA nor toxicity to 2.2.15 cells was observed. CONCLUSION: DrzBS and DrzBC can block the expression of HBV s- and e-genes in 2.2.15 cells and provide a specific and effective anti-HBV gene therapeutic means.