利拉鲁肽对糖尿病合并脂肪肝大鼠的脂代谢相关基因表达的影响  

Effects of liraglutide on expressions of lipid metabolism-related genes in rats with T2DM and fatty liver

作　　者：朱红霞[1] 邓晓龙[1] 高静[1] 李晓岚[1] 王伟[2] 王敏哲[1] 

机构地区：[1]新疆医科大学第五附属医院内分泌科,新疆乌鲁木齐830011 [2]新疆医科大学第五附属医院药剂科,新疆乌鲁木齐830011

出　　处：《中国临床研究》2017年第1期7-10,共4页Chinese Journal of Clinical Research

基　　金：新疆维吾尔自治区自然科学基金(2015211C182)

摘　　要：目的探讨长效人胰升糖素样肽-1(GLP-1)类似物-利拉鲁肽对2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)大鼠的脂代谢相关基因mRNA表达的影响。方法健康雄性8周龄SD大鼠36只,按随机数字表法分为三组(每组12只):正常对照组(NC组)、模型组(MC组)及GLP组。NC组喂以常规饲料;MC组喂以高脂高糖饲料,并一次性腹腔注射链脲佐菌素(STZ,30 mg/kg);GLP组喂以高脂高糖饲料,并一次性腹腔注射STZ(30 mg/kg)及腹部皮下注射利拉鲁肽(0.4 mg/kg,1次/d),三组时限均为4周;MC组和GLP组均在一次性注射STZ 4周后检测血糖,判断是否成功建立T2DM模型。取肝组织病理切片,HE染色后光镜下观察肝细胞脂肪变性情况。采用实时荧光定量PCR方法检测肝脏组织脂代谢相关靶基因-脂肪酸合酶(FAS)、乙酰辅酶A羧化酶(ACC-a)、载脂蛋白β100(apoβ100)的mRNA表达,并检测糖脂代谢相关生化指标。结果 MC组及GLP组各成功建立T2DM模型大鼠11只及12只。NC组未见肝细胞脂肪变性,MC组、GLP组均见明显肝细胞脂肪变性,但GLP组程度明显低于MC组。GLP组大鼠血浆空腹血糖(FBG)和空腹胰岛素(FINS)水平,血浆总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和游离脂肪酸(FFAs)水平均较MC组明显降低,高密度脂蛋白胆固醇(HDL-C)水平则较MC组明显升高(P均<0.05);与NC组比较,MC组与GLP组大鼠肝组织FAS、ACC-a mRNA相对表达量均显著升高(P均<0.01),而GLP组上述指标明显低于MC组(P均<0.01);MC组与GLP组大鼠肝组织apoβ100相对表达量均低于NC组(P均<0.01),但GLP组高于MC组(P<0.01)。结论利拉鲁肽可能通过下调脂代谢相关基因的表达,从而改善脂质代谢紊乱,减缓NAFLD发病的进程。Objective To investigate the effects of liraglutide, a long acting human glucagon like peptide -1 （ GLP-1 ） analogues ,on the expression of lipid metabolism -related genes mRNAs in rats with type 2 diabetes （T2DM） combined with nonalcoholic fatty liver disease （NAFLD）. Methods According to the random number table method, 36 healthy male 8 weeks SD rats were divided into three groups （n = 12 each） ：normal control group （NC group） ,model group （MC group） and GLP group. In NC group, the rats were fed with regular diet. In MC group, the rats were fed with high fat and sugar diet and treated with intraperitoneal injection of sheptozotocin （STZ） one-time （ 30 mg/kg）. In GLP group, the rats were fed with high fat and high sugar diet and treated with intraperitoneal injection of STZ one-time （30 mg/kg） plus abdominal subcutaneous injection of liraglutide（0.4 mg/kg,once a day）. The time of treatment was all 4 weeks in 3 groups. The blood glucose levels in MC group and GLP group were detected 4 weeks after injection of STZ one-time to judge whether the T2DM models were successfully established. Taking section of liver tissue, fatty degeneration of liver cells was observed under light microscope after HE staining. Real-time quantitative polymerase chain reaction was used to detect the expressions of lipid metabolism -related target genes [ fatty acid synthase （ FAS）, acetyl CoA carboxylase （ ACC-a）, apolipoprotein [3100 （ apo β100） ] mRNAs in liver tissues. Biochemical parameters related to glucose and lipid metabolism were detected. Resuits T2DM model was established in 11 rats of MC group and 12 rats of GLP group. No fatty degeneration of liver cells was found in NC group. The fatty degeneration of liver cells was found in both MC group and GLP group, but the degree of fatty degeneration in GLP group was significantly descended compared with MC group（ P 〈 0.05 ）. The relative expression levels of FAS and ACC-a mRNAs in liver tissues in MC group and GLP group sig

关 键 词：长效人胰升糖素样肽-1类似物 2型糖尿病 非酒精性脂肪肝 脂代谢 基因 脂肪酸合酶 乙酰辅酶A羧化酶 载脂蛋白β100 

分 类 号：R587.1[医药卫生—内分泌] R-33[医药卫生—内科学]