疏肝健脾方药对非酒精性脂肪性肝病大鼠Kupffer细胞SREBP-1c信号通路相关基因及蛋白表达的影响  

Effects of soothing liver and invigorating spleen recipes on SREBP-1c signal pathway related genes and proteins in Kupffer cells of nonalcoholic fatty liver disease rats

作　　者：韩莉[1] 杨钦河[2] 张玉佩[2] 徐拥建[2] 刘益臻[2] 杨雪松[3] 金玲[1] 

机构地区：[1]暨南大学附属第一医院,广东广州510632 [2]暨南大学医学院中医系,广东广州510632 [3]暨南大学医学院组织学与胚胎学教研室,广东广州510632

出　　处：《中成药》2014年第5期885-892,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(81173216)

摘　　要：目的观察疏肝健脾方药对非酒精性脂肪性肝病(NAFLD)大鼠Kupffer细胞固醇调节元件结合蛋白-1c(SREBP-1c)信号通路相关基因及蛋白表达的影响及可能的机制。方法采用高脂饲料喂养复制大鼠NAFLD模型,各药物干预组灌饲相应的疏肝健脾方药,8周后检测血液常规生化指标,观察肝组织病理形态改变;采用离体循环灌注Ⅳ型胶原酶法提取肝脏Kupffer细胞,Q-PCR及Western blot法检测Kupffer细胞SREBP-1c、硬脂酰辅酶A去饱合酶-1(SCD-1)mRNA及蛋白表达水平。结果模型组大鼠肝脏脂肪蓄积;血脂及Kupffer细胞SREBP-1c、SCD-1mRNA及蛋白表达水平较正常组均显著升高(P<0.01);各药物干预组Kupffer细胞SREBP-1c、SCD-1 mRNA及蛋白表达水平均有不同程度的下调,同时血脂及病理学改变也较模型组有不同程度的改善,以疏肝组作用最为显著(P<0.01)。结论疏肝健脾方药可能是通过抑制Kupffer细胞SREBP-1c/SCD-1信号通路激活,下调血清总胆固醇、甘油三酯合成,减少肝脏脂质沉积,发挥抗NAFLD作用。可推测SREBP-1c、SCD-1 mRNA及蛋白可能是疏肝健脾方药抗NAFLD的有效作用靶点。AIM To explore effects of soothing liver and invigorating spleen recipes on sterol regulatory element binding proteins-1c（ SREBP-1c） signal pathway related genes and proteins in Kupffer cells of nonalcoholic fatty liver disease（ NAFLD） rats,and to study its possible preventive mechanism. METHODS The rats of NAFLD model were induced by feeding a high-fat diet. The treatment groups were given a gavage of soothing liver and invigorating spleen recipes. After treatment for 8 weeks,detecting routine blood biochemical indicator and liver tissue pathological changes,collagenase（ TypeⅣ） was perfused to digest liver tissue with the circulation in vitro to separate Kupffer cells. Real-time Q-PCR and Western blot were used to detect the expression levels of SREBP-1c signal pathway related genes and proteins. RESULTS The model group rats appeared hepatic fat accumulation obviously. Blood lipid and the expression levels of SREBP-1c,stearyl-CoA desaturase-1（ SCD-1） genes and proteins in model group were higher than those in normal group. Compared with the model group,SREBP-1c,SCD-1 genes and proteins decreased in all drug therapy groups. Levels of blood lipid and pathological changes showed different improvements,and the effect of soothing liver recipes was remarkable（ P〈 0. 01）. CONCLUSIONS Soothing liver and invigorating spleen recipes have good effect on NAFLD,which may be due to inhibiting the activation of SREBP-1c / SCD-1 in Kupffer cells,downing serum total cholesterol,triglyceride synthesis,reducing hepatic lipid deposition. SREBP-1c,SCD-1 mRNA and protein may be effective targets for soothing liver and invigorating spleen recipes to treat NAFLD.

关 键 词：疏肝健脾方药 非酒精性脂肪性肝病 固醇调节元件结合蛋白-1C 硬脂酰辅酶A去饱和酶-1 KUPFFER细胞 大鼠 

分 类 号：R285.5[医药卫生—中药学]