甘草酸二铵脂质配位体对非酒精性脂肪性肝病大鼠肝组织AMPK信号通路的影响  

Effects of diammonium glycyrrhizinate lipid ligand on AMPKα signaling pathways in rats with nonalcoholic fatty liver diseases

作　　者：崔小萌 刘欣[1] 史海涛[1] 赵刚[1] 程妍[1] 杨娟[1] 方媛[1] 

机构地区：[1]西安交通大学第二附属医院消化科,西安市710004

出　　处：《实用肝脏病杂志》2017年第1期55-59,共5页Journal of Practical Hepatology

基　　金：2014年天晴肝病研究基金资助项目(TQGB20140095)

摘　　要：目的研究甘草酸二铵脂质配位体(DGLL)对非酒精性脂肪性肝病(NAFLD)大鼠的治疗作用,并探讨其可能的作用机制。方法以高脂饲料喂养建立NAFLD大鼠模型,在造模成功后分别给予DGLL或多烯磷脂酰胆碱(PPC)灌胃16周。采用免疫组化法检测肝组织磷酸化的磷酸腺苷激活蛋白激酶α(P-AMPKα)蛋白表达,采用Real-time PCR法检测肝组织过氧化物酶体增殖物激活受体γ(PPAR-γ)、肉毒碱棕榈酰基转移酶-1(CPT-1)、葡萄糖转运蛋白4(GLUT-4)、酰基辅酶A氧化酶(ACO)、肝脏型脂肪酸结合蛋白(L-FABP)、乙酰辅酶A羧化酶(ACC)m RNA。结果 DGLL组血清瘦素为(3.87±0.38)ng/ml,显著低于模型组【(4.68±0.39)ng/ml,P<0.01】或PPC组【(4.55±0.24)ng/ml,P<0.01】;DGLL组脂联素为(12.27±0.64)μg/ml,显著高于模型组【(10.46±0.28)μg/ml,P<0.01】,但与PPC组【(12.13±0.56)μg/ml,P>0.05】比,无统计学差异;DGLL组大鼠肝组织P-AMPKα蛋白阳性表达面积为(8.38±3.27)%,显著高于模型组【(1.81±0.90)%,P<0.01】或PPC组【(5.50±0.73)%,P<0.05】;DGLL组肝组织PPAR-γ、CPT-1、GLUT-4 m RNA水平分别为(1.07±0.14、0.91±0.05、1.61±0.54),显著高于模型组【分别为(0.26±0.12、0.14±0.01、0.10±0.03,P<0.05】,但ACO m RNA水平(0.23±0.09)与模型组比,无统计学差异【(0.24±0.02),P>0.05】;PPC组PPAR-γ和CPT-1 m RNA水平分别为(0.65±0.16)和(0.22±0.05),显著低于DGLL组(P<0.05),而GLUT-4和ACO m RNA水平(1.32±0.12和0.14±0.05)与DGLL组比,无统计学差异(P>0.05);DGLL组肝组织ACC m RNA水平为(1.67±0.23),显著低于模型组【(3.31±0.02),P<0.05】或PPC组【(2.69±0.14),P<0.05】;DGLL组L-FABP m RNA水平为(1.06±0.04),显著低于模型组【(1.26±0.02),P<0.05】,而与PPC组【(1.06±0.09),P>0.05】比,无统计学差异。结论 DGLL能降低NAFLD大鼠血脂、血糖、胰岛素、HOMA-IR、瘦素水平,升高脂联素,并增加肝组织P-AMPKα蛋白表达,上调PPAR-γ、CPT-1、GLUT-4 m RNA水平、下调L-FABP和ACC m RNA水Objective To study the therapeutic effect of diammonium glycyrrhizinate lipid ligand （DGLL） on non-alcoholic fatty liver disease（NAFLD） and to explore its possible mechanism. Methods The model of NAFLD was established in rats by feeding high fat diet,and then the DGLL was given with polyene phosphatidylcholine capsules （PPC） as control. Serum liver function index,blood lipids and glucose,insulin,leptin, adiponectin were detected. The expression of P-AMPKα was immunohistochemically assayed,and PPAR-γ,CPT1,GLUT-4,ACO,L-FABP and ACC mRNA were detected by real time PCR. Results The serum levels of leptin in DGLL group were （3.87±0.38） ng/ml,much lower than in the model group [（4.68±0.39） ng/ml,P〈0.01] or in PPC group[（4.55±0.24） ng/ml,P〈0.01];serum adiponectin levels was（12.27±0.64）μg/ml,much higher than in the model【（10.46±0.28）μg/ml,P〈0.01】,while it was not significantly different from in PPC group【（12.13±0.56）μg/ml,P〉0.05】;the P-AMPKα expression area in liver tissue was （8.38±3.27）%,much higher than in the model 【（1.81±0.90）%,P〈0.01】 or in PPC group【（5.50±0.73）%,P〈0.05】;the PPAR-γ,CPT-1,GLUT-4 mRNA in liver tissues were （1.07±0.14,0.91±0.05,1.61±0.54,respectively）,much higher than in the model 【（0.26±0.12, 0.14±0.01, 0.10±0.03,respectivelyt,P〈0.05】,while the ACO mRNA was not significantly different from in the model [（0.23±0.09）vs. （0.24±0.02）,P〉0.05】;the hepatic PPAR-γ and CPT-1 mRNA in PPC group were （0.65±0.16） and （0.22±0.05）,much lower than in DGLL group（P〈0.05）,while the GLUT-4 and ACO mRNA were not significantly different from in the DGLL group（P〉0.05）;the hepatic ACC mRNA in DGLL group was （1.67±0.23）,much lower than in the model【（3.31±0.02）,P〈0.05】 or in the PPC group【（2.69±0.14）,P〈0.05】;the hepatic L-FABP mRNA in DGLL group was（1.06±0.04）,much lower than in the model 【（1.26±0.02）,P〈0.05】,but not significantly diferent

关 键 词：非酒精性脂肪性肝病 甘草酸二铵脂质配位体 多烯磷脂酰胆碱胶囊 磷酸腺苷激活蛋白激酶α 大鼠 

分 类 号：R575.5[医药卫生—消化系统]