脂联素对体外循环心肌胰岛素抵抗模型犬心肌腺苷酸活化蛋白激酶表达的影响
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篇名: 脂联素对体外循环心肌胰岛素抵抗模型犬心肌腺苷酸活化蛋白激酶表达的影响
TITLE:
摘要: 目的:探讨脂联素(APN)对体外循环(CPB)心肌胰岛素抵抗(IR)模型犬心肌腺苷酸活化蛋白激酶(AMPK)表达的影响。方法:将24只犬随机分为对照组、模型组、APN组(36 μg/kg)、AMPK抑制剂组(APN 36 μg/kg+AMPK抑制剂复合制剂C 0.5 mg/kg),每组6只。所有犬行CPB术,除对照组不给药外,其余各组犬建立CPB心肌IR模型,并于主动脉夹闭后灌注不含药或含相应药物的St.Thomas心脏停搏液。分别在CPB转流前和心缺血60 min后再灌注15、90 min收集冠状静脉窦血、颈动脉血,取左心室心尖部组织,测定并计算心肌葡萄糖摄取率和胰岛素抵抗指数(IRI),监测心肌损伤指标[肌钙蛋白T(cTnT)浓度]和心功能指标[左室收缩压(LVSP)、左室内压最大上升速率(+dp/dtmax)]变化,检测磷酸化AMPK(p-AMPK)水平。结果:转流前各组犬之间上述指标差异均无统计学意义(P>0.05)。与对照组比较,模型组犬再灌注15、90 min的心肌葡萄糖摄取率、LVSP、+dp/dtmax和p-AMPK水平均明显降低(P<0.05),IRI和cTnT浓度均明显升高(P<0.05)。与模型组比较,APN组和AMPK抑制剂组犬再灌注15、90 min的心肌葡萄糖摄取率、LVSP、+dp/dtmax和p-AMPK水平均明显升高(P<0.05),IRI和cTnT浓度均明显降低(P<0.05),且APN组效果强于AMPK抑制剂组(P<0.05)。结论:APN可促进心肌对葡萄糖的摄取及代谢以助心功能恢复,其可能是通过增强AMPK活性来发挥效应的。
ABSTRACT: OBJECTIVE: To investigate the effects of adiponectin (APN) on the expression of myocardial AMPK in myocardial insulin resistance (IR) model dogs during cardiopulmonary bypass (CPB). METHODS: Totally 24 dogs were randomly divided into control group, model group, APN group (36 μg/kg), AMPK inhibition group (APN 36 μg/kg+AMPK inhibitor compound C 0.5 mg/kg), with 6 dogs in each group. All dogs underwent CPB; except for control group without medicine, CPB myocardial IR model were established in other groups, and perfused with St.Thomas cardiac cardioplegia lipid no medicine or containing relevant drugs after main artery block. Coronary sinus blood and carotid artery blood samples were collected before bypass and after 15, 90 min reperfusion following 60 min myocardial ischemia. Left ventricular apical tissue was taken, and the uptake rate of myocardial glucose and insulin resistance index (IRI) were determined and calculated; the changes of myocardial injury indexes (cTnT concentration) and cardiac function indexes (LVSP, +dp/dtmax) were monitored. The level of p-AMPK was detected. RESULTS: There was no statistical significance in above indexes of dogs before bypass (P>0.05). Compared with control group, the rate of myocardial glucose uptake, the levels of LVSP, +dp/dtmax and p-AMPK in model group were decreased significantly after 15, 90 min reperfusion (P<0.05), and the concentrations of IRI and cTnT were increased significantly (P<0.05). Compared with model group, the rate of myocardial glucose uptake, LVSP, +dp/dtmax and p-AMPK were increased significantly in APN group and AMPK inhibitor group (P<0.05), while the concentrations of IRI and cTnT were decreased significantly (P<0.05); moreover, the effect of APN group was better than that of AMPK inhibitor group (P<0.05). CONCLUSIONS: APN can promote myocardial glucose uptake and metabolism, and contribute the recovery of cardiac function, the mechanism of which may be associated with increasing the activity of AMPK.
期刊: 2019年第30卷第7期
作者: 张登沈,梁贵友,刘达兴,王峰,潘斯斯,张长江
AUTHORS: ZHANG Dengshen,LIANG Guiyou,LIU Daxing,WANG Feng,PAN Sisi,ZHANG Changjiang
关键字: 脂联素;体外循环;心肌胰岛素抵抗;犬;腺苷酸活化蛋白激酶
KEYWORDS: Adiponectin; Cardiopulmonary bypass; Myocardial insulin resistance; Dog; AMPK
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