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目的探讨载脂蛋白A-I模拟肽(L-4F)改善糖尿病心脏和冠状动脉功能失调的作用及可能机制。方法将20只C57BL/6J小鼠随机分为正常对照组(10只)和L-4F对照组(10只);将20只db/db小鼠随机分为糖尿病组(10只)和L-4F治疗组(10只)。用L-4F或缓冲液治疗8周后,测量各组小鼠血糖、胰岛素及脂联素水平。采用Langendorff装置测量各组小鼠心脏功能和冠状动脉阻力,采用免疫印迹法测定心肌组织中血红素氧合酶-1(heme oxygenase-1,HO-1)、腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)、磷酸化腺苷酸活化蛋白激酶(phosphorylated adenosine monophosphate activated protein kinase,p AMPK)、磷酸化内皮型一氧化氮合酶(phosphorylated endothelial nitric oxide synthase,pe NOS)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)及诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)等基因的表达水平。结果与糖尿病组相比,L-4F治疗组血糖、胰岛素、炎性因子水平明显降低(P<0.05),脂联素水平明显升高(P<0.05),左心室短轴缩短率(left ventricular fractional shortening,LVFS)明显增加(P<0.05),左心室舒张末期内径(left ventricular end diastolic diameter,LVEDD)及左心室收缩末期内径(left ventricular systolic diameter,LVESD)明显减小(P<0.05),心肌组织中的HO-1、p AMPK、pe NOS表达水平明显升高(P<0.05),i NOS和过氧化物表达水平明显降低(P<0.05)。低压缺血期糖尿病组(8.83±0.08)和正常对照组(6.41±0.05)冠状动脉阻力均增加,糖尿病组持续增加更为显著,且均明显高于L-4F治疗组(5.15±0.04,P<0.01)和L-4F对照组(4.96±0.03,P<0.01)。结论 L-4F能够上调HO-1表达水平,增加脂联素、p AMPK、pe NOS的表达水平,提高抗氧化应激、抗炎性反应并改善血管内皮功能,达到改善糖尿病心脏及冠状动脉功能的目的。
Objective To investigate the effects and possible mechanisms of apolipoprotein A-I mimetic peptide (L-4F) on dysfunction of heart and coronary artery in diabetic patients. Methods 20 C57BL / 6J mice were randomly divided into normal control group (n = 10) and L-4F control group (n = 10); 20 db / db mice were randomly divided into diabetic group 4F treatment group (10). After treatment with L-4F or buffer for 8 weeks, the blood glucose, insulin and adiponectin levels in each group were measured. The cardiac function and coronary resistance of mice in each group were measured by Langendorff apparatus. The expression of heme oxygenase-1 (HO-1), adenosine monophosphate activated protein kinase (AMPK), phosphorylated adenosine monophosphate activated protein kinase (p AMPK), phosphorylated endothelial nitric oxide synthase (pe NOS) The expression of eNOS and inducible nitric oxide synthase (iNOS) and other genes was also examined. Results Compared with diabetic group, the levels of blood glucose, insulin and inflammatory cytokines in L-4F treatment group were significantly decreased (P <0.05), and adiponectin level was significantly increased (P <0.05), left ventricular shortening rate (P <0.05). The left ventricular end diastolic diameter (LVEDD) and left ventricular systolic diameter (LVESD) were significantly decreased (P <0.05) The levels of HO-1, p AMPK and pe NOS in myocardium were significantly increased (P <0.05), and the levels of iNOS and peroxide were significantly decreased (P <0.05). Coronary resistance was significantly increased in the diabetic group (8.83 ± 0.08) and in the normal control group (6.41 ± 0.05), and the diabetic group continued to increase more significantly than the L-4F group (5.15 ± 0.04, P <0.01) and L-4F control group (4.96 ± 0.03, P <0.01). Conclusions L-4F can up-regulate the expression of HO-1, increase the expression of adiponectin, p-AMPK and pe NOS, increase the anti-oxidative stress and anti-inflammatory reaction and improve endothelial function and improve the function of diabetic heart and coronary artery the goal of.