ABSTRACT
Objective To investigate the efficacy of sophocarpine in rats with alcoholic liver disease and its effects on the expression of tumor necrosis factor (TNF)-α,interleukin (IL)-6 and transforming growth factor (TGF)-β1.Methods A total of 48 male Sprague-Dawley adult rats were evenly divided into healthy control group,model group,prevention group and treatment group.The rats in the healthy control group were gavaged with 0.9％NaCl every day for 12 weeks.The rats in the model group,prevention group and treatment group were gavaged with alcohol for 12 weeks to establish the model.The prevention group was injected with 20 mg · kg1 · d1 sophocarpine for 12 weeks.Since the fifth week,the treatment group was continuously injected with 20 mg · kg1 · d-1 sophocarpine for eight weeks.The histological changes were evaluated.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase ( AST ), alkaline phosphatase (AKP),triglyceride (TG) and total cholesterol (TC) were examined.And the expression of TNF-α,IL-6 and TGF-β1 in liver tissue at mRNA and protein level were detected with immunohistochemistry and real-time polymerase chain reaction (PCR) assay.Comparison among groups was perform with single factor analysis of variance,pairwise comparisons with least significant difference method (LSD method),ranked data with Kruskal-Wallis H-test and multiple pairwise comparison with Nemenyi test.Results Compared with model group,hepatic steatosis and inflammatory cell infiltration were significantly improved in the treatment group and prevention group.The levels of ALT (41.40 U/L± 10.53 U/L and 40.75 U/L±6.94 U/L vs 58.37 U/I±5.35 U/L),AST(121.60 U/L±16.24 U/L and 109.50 U/L±9.23 U/L vs 156.63 U/L±32.47 U/L),AKP(114.88 U/L±40.37 U/L and 112.60 U/L±44.34 U/L vs 161.75 U/L±28.95 U/L),TG (4.19 mmol/L±0.99 mmol/L and 2.69 mmol/L± 1.35 mmol/L vs 4.50 mmol/L±0.99 mmol/L) and TC (1.48 mmol/L±0.28 mmol/L and 1.43 mmol/L±0.19 mmol/L vs 1.67 mmol/L±0.20 mmol/L) significantly decreased and the difference was statistically significant ( all P＜0.05).The expression of TNF-α,IL-6 and TGF-β1 at mRNA and protein level in liver tissue of model group were significantly higher than those of healthy control group,prevention group and treatment group.After treated with sophocarpine,the expression of TNF-α(mRNA:1.36 ± 0.08,1.16 ± 0.05 ; protein:3.38 ％ ± 0.82 ％,1.74 ％ ± 0.65 ％ ),IL-6 (mRNA:1.51 ± 0.05,1.39 ± 0.02; protein:5.89％ ± 0.96％,4.26％ ± 0.53％) and TGF-β1 (mRNA:1.39±0.04,1.37±0.02; protein:4.27％ ±0.97％,2.11％ ±0.83％) of treatment group and prevention group at mRNA and protein level significantly lower than those of model group (mRNA:1.81±0.16,1.95 ±0.13,1.84±0.22; protein:5.82％ ± 1.21％,7.63％ ±1.03％,5.33％± 1.12％) and the difference was statistically significant (all P＜0.01).Conclusion Sophocarpine significantly alleviates alcohol induced liver injury in rats,improves liver steatosis and inflammatory reaction degree,which may be related with the downregulation of TNF-α,TGF-β1 and IL-6 expression in liver tissue of ALD rats.
ABSTRACT
AIM To study the cancer promoting effects of N nitrosodiethylamine (DEN) and 2 Acetylaminofluorene (2 AAF). METHODS Medium Term Rat Liver Bioassay (MTRLB). Male SD rats were initially given a single dose (200 mg?kg -1 ) of DEN ip and starting 2 weeks later, were treated with 10, 33 and 100 ppm DEN in drinking water, or with 2 2, 6 6 and 22 mg?kg -1 2 AAF by gavage for 6 weeks. All rats were subjected to two thirds partial hepatectomy at week 3 and killed at the end of week 8. Carcinogenic potential was scored by comparing the numbers and areas in induced glutathione S transferase placental form (GST P) positive foci in the liver with those of corresponding control group given DEN alone. RESULTS Both DEN and 2 AAF caused the increases of the numbers and areas of GST P positive foci in the liver, and showed dose response relationship. CONCLUSION Both DEN and 2 AAF shows cancer promoting effects, and MTRLB was a convenient, economical and effective tool to study the cancer promoting effects of test chemicals.