白花丹醌对肝纤维化大鼠磷脂酰肌醇3-激酶／蛋白激酶B信号转导通路的影响  

Influences of plumbagin on phosphatidylinositol 3-kinase/protein kinase B signaling pathway in rats with hepatic fibrosis

作　　者：陈小维[1] 张伟伟[1] 陈金霞[1] 张友才[1] 陈永平[1] 李骥[1] 

机构地区：[1]温州医学院附属第一医院感染科,325000

出　　处：《中华传染病杂志》2013年第9期519-523,共5页Chinese Journal of Infectious Diseases

摘　　要：目的研究白花丹醌对四氯化碳所致肝纤维化大鼠磷脂酰肌醇3-激酶（P13K）／蛋白激酶B（Akt）信号转导通路的影响。方法40只雄性SD大鼠分成对照组、模型组、2mg／kg白花丹醌处理组和3mg／kg白花丹醌处理组，每组10只。对照组予0．9％氯化钠溶液2mL／kg腹腔注射，其余3组均予60％四氯化碳花生油溶液2mL／kg腹腔注射，均每周3次，共6周。造模后第3周开始，白花丹醌处理组分别给予2mg／kg和3mg／kg白花丹醌花生油剂腹腔注射，每周2次，共4周。常规检测大鼠血清ALT、AST、Alb，放射免疫法测定HA和LN，Western印迹检测肝组织中P13K、Akt和磷酸化蛋白激酶B（p—Akt）蛋白表达量，免疫组织化学法检测p-Akt表达。各组间均数比较采用单因素方差分析。结果6周后成功建立肝纤维化大鼠模型。模型组大鼠ALT、AST、HA和I。N均高于对照组，2mg／kg白花丹醌处理组和3mg／kg白花丹醌处理组中的ALT、AST、HA和LN水平较模型组下降，差异均有统计学意义（均P〈0．05）。各组P13K、Akt蛋白表达差异均无统计学意义（均P〉0．05）；P—Akt蛋白表达主要集中在肝细胞核；对照组、模型组、2mg／kg白花丹醌处理组和3mg／kg白花丹醌处理组大鼠p-Akt蛋白分别为0．0821±0．0003、0．7374±0．0037、0．3679±0．0332和0．1327±0．0561，模型组表达高于对照组（t=851．302，P〈0．05），白花丹醌处理后下降（t值分别-71．858和28．363，均P〈0．05）。结论白花丹醌具有抗肝纤维化作用。白花丹醌可下调肝纤维化过程中p-Akt的表达，这可能是其抗肝纤维化的机制之一。[Abstract] Objective To explore the influences of plumbagin on phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway in rats with carbon tetrachloride induced liver fibrosis. Methods Forty male SD rats were assigned to control group, model group, 2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group, with 10 rats in each group. Rats of the control group were injected with 0.9 ~ NaC1 solution （2 mL/kg） intraperitoneally, while rats of the other three groups were injected with 60% carbon tetrachloride/peanut oil （2 mL/kg, 3 times a week for 6 weeks） intraperitoneally. Since the third week after modeling, rats of plumbagin treated groups were treated with intraperitoneal injection of plumbagin at a dose of 2 mg/kg and 3 mg/kg （twice a week for 4 weeks）, respectively. Serum levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin （Alb） were monitored routinely. Hyaiuronic acid （HA） and laminin （LN） were measured by radioimmunoassay after 6 weeks; protein expression of liver PI3K, Akt and phosphorylated Akt （p-Akt） were evaluated by Western blotting and immunohistochemistry, respectively. Comparison of means among groups was performed hy univariate analysis of variance. Results The hepatic fibrosis model was successfully established after 6 weeks. Serum levels of ALT, AST, HA and LN of model group were significantly higher than those of control group （all P 0.05）. Serum levels of ALT, AST, HA and LN of 2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group were significantly lower than those of model group, and the differences were statistically significant （all P〈0.05）. The protein expressions of PI3K and Akt in each group were comparable （all P）0.05）. The p Akt protein was mainly expressed in nucleus of hepatocytes. The levels of p-Akt protein in control group, model group, 2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group were 0. 0821±0. 0003, 0. 737±0. 0037,

关 键 词：肝硬化 白花丹 醌类 1-磷脂酰肌醇3-激酶 蛋白激酶类 信号传导 大鼠  Sprague—Dawley 

分 类 号：R285.5[医药卫生—中药学]