槐果碱对大鼠酒精性肝病的作用及机制  

Effects and mechanism of sophocarpine in rats with alcoholic liver disease

作　　者：乔春萍[1] 施建平[1] 叶慧英[2] 高仁里[2] 顾国妹[1] 何峻峰[1] 陈岳祥[3] 

机构地区：[1]复旦大学附属华山医院南汇分院消化科,上海201300 [2]复旦大学附属华山医院病理科,上海201300 [3]上海长征医院消化科

出　　处：《中华消化杂志》2012年第8期543-548,共6页Chinese Journal of Digestion

基　　金：上海市浦东新区卫生局卫生科技发展专项基金（PW2011A-23）

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、转化生长因子一β1（TGF-β1）和IL一6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20mg·kg-1·d-1共12周，治疗组第5周起连续8周注射槐果碱20mg·kg-1·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—WallisH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／L3、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]、TGl（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～amRNA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-6mRNA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-β mRNA和蛋白表达水平[mRNA：1．39±0．04，1．37土0．02；蛋白：（4．27Objective 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 NaC1 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·kg-1·d-1 sophocarpine for 12 weeks. Since the fifth week, the treatment group was continuously injected with 20mg·kg-1·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 immunohistoehemistry 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 eell 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/L±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（l14.88 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/L0. 28 mmol/L and 1.43 mmol/L±0. 19

关 键 词：肝疾病 酒精性 生物碱类 肿瘤坏死因子α 白细胞介素6 转化生长因子β1 

分 类 号：R285.5[医药卫生—中药学]