载脂蛋白A-Ⅰ模拟肽对代谢综合征大鼠心功能的可能影响及作用机制  

Effect of apolipoprotein A1 mimetic peptide on cardiac function in rats with metabolic syndrome and its mechanism

作　　者：郭玉松 柯瑟章 高进辽[3] 刘璐[3] 李瑞生[4] 黄鑫[3] 邹晓[3] 范利[3] 曹剑[3] Guo Yusong;Ke Sezhang;Gao Jinliao;Liu Lu;Li Ruisheng;Huang Xin;Zou Xiao;Fan Li;Cao Jian(Department of Geriatrics,Chinese PLA 309 Hospital,Beijing 100091,China)

机构地区：[1]解放军第三〇九医院第二干部病房,北京100091 [2]福建医科大学附属漳州市医院干部病房 [3]解放军总医院南楼心血管内科,国家老年疾病临床医学研究中心 [4]解放军第三〇二医院实验技术研究保障中心

出　　处：《中华老年心脑血管病杂志》2018年第11期1138-1143,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81270154);军队保健专项(16BJZ15);解放军第三〇九医院面上课题(2017MS-002).

摘　　要：目的探讨载脂蛋白A-Ⅰ模拟肽(L4F)对于代谢综合征(MS)大鼠通过血红素氧合酶1(HO-1)发挥作用的可能机制。方法选取大鼠60只分为对照组(20只)与MS组(40只),分别给予普通饲料与高果糖饲料喂养6周,每组各取10只行心脏超声及血流动力学检测后处死,对照组剩余10只给予碳酸铵缓冲溶液(ABCT);MS组剩余30只大鼠随机分为ABCT组、L4F组及抑制剂组,每组10只,分别给予ABCT、L4F、L4F+抑制剂,继续喂养6周,检测心肌脂联素、HO-1、磷酸化腺苷酸活化蛋白激酶(p-AMPK)、磷酸化蛋白激酶B(p-Akt)、磷酸化内皮型一氧化氮合酶(p-eNOS)表达。结果 MS组血糖、收缩压、舒张压及左心室舒张末期内径显著高于对照组(P<0.05,P<0.01)。与抑制剂组比较,L4F组血压、血糖、左心室舒张末压明显降低;脂联素、p-AMPK、p-Akt、p-eNOS表达显著升高(P<0.05)。L4F组HO-1表达与抑制剂组相近(P>0.05)。结论L4F可能是通过作用于能量代谢通路HO-1、脂联素、p-AMPK、p-Akt、p-eNOS上调HO-1的表达,降低MS大鼠血压和血糖,改善心室顺应性。Objective To study the effect of apolipoprotein A1 mimetic peptide(L4 F)on cardiac function in rats with MS by activating HO-1 and its mechanism.Methods Sixty rats were divided into control group(n=20)and MS group(n=40).The animals in 2 groups were fed on common forages and high-fructose forages respectively for 6 weeks,10 rats from each group were killed after they underwent cardiac ultrasonography and hemodynamic testing.The other 10 animals in control group were treated with ABCT.The other 30 animals in MS group were randomly divided into ABCT group(n=10),L4 Fgroup(n=10),L4 Finhibitor group(n=10)and fed on forages for additional 6 weeks.Expressions of APN,HO-1,p-AMPK,p-Akt,p-eNOS were detected.Results The SBP,DBP and blood glucose were significantly higher and the left ventricular end diastolic diameter was significantly longer in MS group than in control group(P<0.05,P<0.01).The left ventricular end diastolic pressure was significantly lower while the expression levels of APN,p-AMPK,p-Akt,p-eNOS were significantly higher in L4 Fgroup than in L4 Finhibitor group(P<0.05).Conclusion L4 Fcan reduce the blood pressure and blood glucose,improve the ventricular compliance in MS model of rats by upregulating the expression and activity of HO-1 and activating the energy metabolism pathways of HO1-APN-pAMPK-pAkt-peNOS.

关 键 词：载脂蛋白A-Ⅰ 胰岛素抗药性 肥胖症 高血压 血红素加氧酶-1 

分 类 号：R589[医药卫生—内分泌]