黄连解毒汤通过抑制TGF-β信号通路减轻2型糖尿病大鼠肝脂肪变性和纤维化研究  

Huanglian Jiedu decoction alleviates hepatic steatosis and fibrosis in type 2 diabetic rats through activation of TGF-βsignaling pathway

作　　者：苟芳[1] 张红军[1] 王洁 张邱兵 GOU Fang;ZHANG Hongjun;WANG Jie;ZHANG Qiubing(Guangyuan Central Hospital,Guangyuan 628000,China)

机构地区：[1]广元市中心医院,四川广元628000 [2]西南医科大学附属医院,四川泸州646000

出　　处：《陕西中医》2022年第2期170-176,共7页Shaanxi Journal of Traditional Chinese Medicine

基　　金：四川省医学科研青年创新课题(Q15042)。

摘　　要：目的:探讨黄连解毒汤对2型糖尿病大鼠肝脂肪变性和纤维化的保护作用。方法:取30只SD大鼠随机分为空白对照组(NC组)、糖尿病模型组(DM组)和黄连解毒汤组(HL组),每组各10只。造模6周后,对各组大鼠的体重、肝指数、血清生化指标以及肝脏的病理学改变进行比较。结果:①与NC组大鼠相比,DM组大鼠的体重增长量较小,但食物和水的摄入量明显增加。HL组大鼠治疗后大鼠的体重增长量有所增加,并改善了糖尿病大鼠的多饮和多食。油红O染色显示,DM组大鼠肝内有大量脂质沉积。大量脂肪变性肝细胞在中央静脉周围呈斑点状分布,HL干预后在很大程度上改变了这种脂质分布,中央静脉周围有较轻的脂肪变性肝细胞聚集。②天狼星红染色发现,DM组的Ⅰ型和Ⅲ型胶原水平明显高于NC组,而HL治疗的糖尿病大鼠肝脏的Ⅰ型和Ⅲ型胶原水平显著降低。③与DM组相比,HL治疗有效地降低了糖异生基因糖异生关键酶Pck1和G6P基因的表达水平。与NC组大鼠相比,成脂关键基因如固醇调节元件结合蛋白1c(Srebp1c)和硬脂酰辅酶A去饱和酶1(Scd1)显著上调,而β氧化关键基因,如过氧化物酶酰基辅酶A氧化酶2(ACOX2)和肉碱棕榈酰转移酶1(Cpt1)基因表达下调。④免疫组化染色显示,DM组转化生长因子-β(TGF-β)阳性细胞明显增多,主要分布于汇管区、纤维间隙。与DM组比较,HL组TGF-β表达降低,差异有统计学意义(P<0.05)。Western blot检测显示,HL干预可显著抑制糖尿病肝组织中高度激活的TGF-β/Smad2/3信号通路(P<0.05)。结论:黄连解毒汤可减轻氧化应激和抑制炎症,减轻2型糖尿病大鼠的肝脏脂质沉积和肝纤维化,这可能与抑制NF-κB介导的炎症通路和抑制TGF-β/Smad信号通路有关。Objective:To investigate the protective effect and mechanism of Huanglian Jiedu decoction on hepatic steatosis and fibrosis in type 2 diabetic rats.Methods:Thirty SD rats were randomly divided into NC group,DM group and HL group,10 rats in each group.The body weight,liver index,serum biochemical indexes and pathological changes of liver in each group were compared.Results:①Compared with NC group,the weight gain of DM group was significantly smaller,but the intake of food and water was significantly increased.After treatment,the weight gain of HL group was increased,and the polydipsia and overeating of diabetic rats were improved.There were a lot of lipid deposition in the liver of DM group.A large number of steatotic hepatocytes were spotted around the central vein,which was changed to a great extent by HL intervention.②The levels of typeⅠand typeⅢcollagen in DM group were significantly higher than those in NC group,while the levels of typeⅠandⅢcollagen in liver of diabetic rats treated with HL were significantly lower.③Compared with DM group,HL treatment effectively reduced the expression levels of Pck1 and G6P genes.Compared with NC group,the expression of Srebp1c and Scd1 was significantly up-regulated,while the expression of ACOX2 and Cpt1 was down regulated.④In DM group,TGF-βpositive cells increased significantly,mainly distributed in the portal area and fibrous space.The expression of TGF-βin HL group was significantly lower than that in DM group(P<0.05).HL intervention significantly inhibited TGF-β/Smad2/3 signaling pathway in diabetic liver tissue(P<0.05).Conclusion:Huanglian Jiedu decoction can reduce liver lipid deposition and liver fibrosis in type 2 diabetic rats by reducing oxidative stress and inhibiting inflammation,which may be related to inhibiting NF-κB-mediated inflammatory pathway and inhibiting TGF-β/Smad signaling pathway.

关 键 词：糖尿病 肝损伤 黄连解毒汤 转化生长因子-Β 肝脂肪变性 肝纤维化 

分 类 号：R587.1[医药卫生—内分泌]