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目的建立大鼠心肌缺血/再灌注损伤(MIRI)模型,探讨利拉鲁肽对心肌损伤的保护作用和机制。方法可逆性冠脉左前降支结扎造成MIRI模型,给予大鼠心脏缺血30 min再灌注90 min。30只雄性SD大鼠随机分为3组,分别为假手术组、MIRI模型组和利拉鲁肽干预组(70μg/kg)。干预组每天1次,连续7 d。彩色多普勒超声仪测定心脏功能,Millar导管法测定血流动力学指标,腹主动脉插管取血,离心制备血清,自动生化分析仪测血清天冬氨酸氨基转换酶(AST)、肌酸激酶同工酶(CK-MB)及乳酸脱氢酶(LDH)活力;酶联免疫吸附试验(ELISA)法测定血清炎性因子含量白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF-α);实时荧光定量PCR检测各组心肌组织细胞凋亡相关基因Bax,Bcl-2和Caspase3,9 m RNA的表达。结果与模型组相比,利拉鲁肽可明显加快大鼠心率(HR),提升动脉收缩压(SBP)、舒张压(DBP)和左心室收缩压(LVSP)(P<0.05),使左心室舒张末压(LVEDP)有所降低(P<0.05);相比模型组,利拉鲁肽干预组心肌酶活力均显著降低(P<0.05),且可使模型组大鼠血清炎性因子含量降低,利拉鲁肽干预组大鼠心肌Bax、Caspase3 m RNA表达水平显著降低,Bcl-2 m RNA表达水平显著升高。结论利拉鲁肽可通过减少炎性因子和细胞凋亡相关基因,抑制心肌细胞的损伤和凋亡作用,从而对大鼠MIRI有一定的保护作用。
Objective To establish a myocardial ischemia / reperfusion injury (MIRI) model in rats and explore the protective effect and mechanism of liraglutide on myocardial injury. Methods Reversible left anterior descending coronary artery ligation caused MIRI model, giving 30 min ischemia reperfusion in rat heart for 90 min. Thirty male Sprague-Dawley rats were randomly divided into three groups: sham operation group, MIRI model group and liraglutide intervention group (70μg / kg). Intervention group 1 day, for 7 days. The color Doppler was used to measure the cardiac function. The Millar catheter method was used to measure the hemodynamics index. The abdominal aorta catheter was used to take the blood. The serum was prepared by centrifugation. The levels of serum aspartate aminotransferase (AST) (CK-MB) and lactate dehydrogenase (LDH) were detected by enzyme linked immunosorbent assay (ELISA). Serum levels of inflammatory cytokines IL-1β, IL-6 and tumor necrosis (TNF-α). The expression of Bax, Bcl-2, Caspase 3,9 m RNA in cardiac myocytes were detected by real-time fluorescence quantitative PCR. Results Compared with the model group, liraglutide significantly accelerated heart rate (HR), increased systolic pressure (SBP), diastolic pressure (DBP) and left ventricular systolic pressure (LVSP) LVEDP decreased (P <0.05). Compared with the model group, the activity of myocardial enzymes in liraglutide intervention group was significantly lower (P <0.05), and the level of serum inflammatory cytokines The expression of Bax and Caspase3mRNA in the myocardium of liraglutide intervention group decreased significantly, and the expression level of Bcl-2 mRNA increased significantly. Conclusion Liraglutide could inhibit the injury and apoptosis of cardiomyocytes by reducing the expression of inflammatory cytokines and apoptosis related genes, which may have a protective effect on MIRI in rats.