基于PPAR-γ和TLR-4/NF-κB信号通路研究狗肝菜多糖对非酒精性脂肪性肝大鼠的保护作用机制  

Protective Effect and Mechanism of Dicliptera Chinensis Polysaccharides on Non-Alcoholic Fatty Liver Disease in Rats Based on PPAR-γ and TLR-4/NF-κB Signaling Pathway

作　　者：张可锋 晋玲[1] Zhang Kefeng;Jin Ling(College of pharmacy,Gansu university of traditional Chinese medicine,Lanzhou 730000;College of pharmacy,Guilin medical school,Guilin 541004)

机构地区：[1]甘肃中医药大学药学院,兰州730000 [2]桂林医学院药学院,桂林541004

出　　处：《中药药理与临床》2019年第4期103-107,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81360685、81760114、81660104);广西区自然科学基金(2017GXNSFAA198218、2018GXNSFAA281040)

摘　　要：目的:研究狗肝菜多糖对非酒精性脂肪性肝(NAFLD)大鼠的保护作用,并探索其作用机制。方法:46只SD大鼠分为正常组(13只)和高脂饲料组(33只),8 w后每组各随机抽取3只,病理检查确定NAFLD模型成功后,再将高脂饲料组分为模型组和狗肝菜多糖100、200 mg/kg组,每组10只。从第9周起,各组灌胃给予相应药物或生理盐水6 w,采用生化法检测血清中ALT和AST的活性以及肝组织中MDA、SOD和GSH-Px含量;酶联免疫吸附法检测肝组织中TNF-α、IL-6和IL-1β含量;采用苏木精-伊红(HE)染色观察大鼠肝组织病理学变化;采用蛋白质印迹法(Western blot)检测大鼠肝组织中过氧化物酶体增殖物激活受体-γ(PPAR-γ)、Toll样受体4(TLR-4)和磷酸化NF-κB p65蛋白表达情况。结果:与正常组相比,模型组大鼠血清中ALT和AST活性以及肝组织中MDA、TNF-α、IL-6和IL-1β含量均显著升高;肝组织中SOD和GSH-Px活性均显著降低;肝组织中PPAR-γ表达下调,TLR-4和磷酸化NF-κB p65蛋白表达均显著上调。与模型组比较,狗肝菜多糖各剂量组大鼠血清中ALT和AST活性以及肝组织MDA、TNF-α、IL-6和IL-1β含量均明显降低,肝组织SOD和GSH-Px活性均明显增强;肝组织PPAR-γ表达上调,TLR-4和磷酸化NF-κB p65蛋白表达量均下调。结论:狗肝菜多糖对NAFLD大鼠有一定的保护作用,其机制可能与调节PPAR-γ和TLR-4/NF-κB信号通路有关。Objective: To study the protective effect of Dicliptera chinensis polysaccharide on rats with non-alcoholic fatty liver disease (NAFLD)and its mechanism. Methods: 46 SD rats were randomly divided into the control group (13 rats) and high-fat diet group (33 rats). After 8 weeks of feeding high-fat diet,3 rats were randomly selected from each group and pathological examination were used to confirm the NAFLD model establishment. After modeled,rats in high-fat diet group were randomly divided into the model group and Dicliptera chinensis polysaccharide groups (100,200 mg/kg),10 in each group. From week 9,all rats were administered with corresponding drugs or saline water,for6 weeks. The activities of ALT and AST in serum and the contents of MDA,SOD and GSH-Px in liver tissues were detected by biochemical method. The contents of TNF-α,IL-6 and IL-1β in liver tissues were determined by ELISA. The histopathological changes of rat livers were observed by hematoxylin-eosin (HE) staining. The expressions of peroxisomal proliferators activated receptor-γ (PPAR-γ),toll like receptor 4 (TLR-4) and phosphorylated NF-κB p65 in rat livers were detected by Western blot. Results: Compared with the control group,the serum ALT and AST activities and the contents of MDA,TNF-α,IL-6 and IL-1β in the liver tissues in the model group were significantly increased. The activities of SOD and GSH-Px in liver tissues were significantly decreased. The expression of PPAR-γ was decreased,and theexpressions of TLR-4 and phosphorylated NF-κB p65 protein were significantly increased. Compared with the model group,the serum ALT and AST activities,as well as the contents of MDA,TNF-α,IL-6 and IL-1β in liver tissues were decreased in both Dicliptera chinensis polysaccharide groups,the activities of SOD and GSH-Px in liver tissues were enhanced. The expression of PPAR-γ was increased,the expression of TLR-4 and phosphorylated NF-κB p65 was decreased. Conclusion: Dicliptera chinensis polysaccharide has a protective effect on NAFLD rats,its

关 键 词：狗肝菜多糖 非酒精性脂肪性肝 PPAR-Γ TLR-4/NF-κB信号通路 

分 类 号：R28[医药卫生—中药学]