摘要目的 探讨槐果碱对大鼠酒精性肝病(ALD)的疗效及其对TNF-α、转化生长因子-β1( TGF-β1)和IL-6表达的影响.方法 48只SD大鼠均分为健康组、模型组、预防组、治疗组,健康组每日予0.9％ NaCl溶液灌胃12周,模型组、预防组、治疗组大鼠予乙醇灌胃造模12周,预防组同时注射槐果碱20 mg·kg-1·d-1共12周,治疗组第5周起连续8周注射槐果碱20 mg·kg1·d-1.评价肝组织学病变,检测ALT、AST、碱性磷酸酶(AKP)、三酰甘油(TG)和总胆固醇(TC)含量,免疫组织化学和实时定量PCR检测肝组织TNF-α、IL-6和TGF-β1 mRNA和蛋白表达.多组间比较采用单因素方差分析,两两比较采用最小显著差法(LSD法),等级资料用Kruskal-Wallis H检验,多组两两比较采用Nemenyi法检验.结果 治疗组和预防组与模型组比较,大鼠肝脏脂肪变和炎性细胞浸润程度明显改善,ALT[(41.40±10.53)U/L和(40.75±6.94)U/L比(58.37±5.35)U/L]、AST[(121.60±16.24)U/L和(109.50±9.23)U/L比(156.63±32.47)U/L]、AKP[(114.88±40.37) U/L和(112.60±44.34) U/L比(161.75±28.95)U/L]、TC[(4.19±0.99)mmol/L和(2.69±1.35)mmol/L比(4.50±0.99)mmol/L]、TG[(1.48±0.28)mmol/L和(1.43±0.19) mmol/L比(1.67±0.20)mmol/L]水平明显下降,差异有统计学意义(P值均＜0.05).模型组大鼠肝组织中TNF-α、IL-6、TGF-β1的mRNA和蛋白表达水平较健康组、预防组、治疗组明显增高.槐果碱干预后,治疗组和预防组的TNF-α mRNA和蛋白表达水平[mRNA:1.36±0.08,1.16±0.05;蛋白:(3.38±0.82)％,(1.74±0.65)％]、IL-6 mRNA和蛋白表达水平[mRNA:1.51±0.05,1.39±0.02；蛋白:(5.89±0.96)％,(4.26±0.53)％]、TGF-β1 mRNA和蛋白表达水平[mRNA:1.39±0.04,1.37±0.02;蛋白:(4.27±0.97)％,(2.11±0.83)％]较模型组[mRNA:1.81±0.16,1.95±0.13,1.84±0.22;蛋白:(5.82±1.21)％,(7.63±1.03)％,(5.33±1.12)％]明显降低,差异有统计学意义(P值均＜0.01).结论 槐果碱能明显减轻乙醇导致的大鼠肝损伤,改善大鼠肝组织脂肪变和炎性反应程度,可能与其下调ALD大鼠肝组织TNF-α、IL-6和TGF-β1的表达有关.

abstractsObjective 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.