摘要
目的:通过建立大鼠心肌缺血再灌注模型,研究吡格列酮对心肌缺血再灌注损伤的保护作用及机制。方法:取心电图无异常的大鼠34只,随机分为T1组和T2组,T1组再分为对照组(n=5)和吡格列酮组(n=5),T2组分为假手数组(n=8)、对照组(n=8)、吡格列酮组(n=8)。假手数组只开胸不结扎冠状动脉。其余各组均结扎冠状动脉30 min,再灌注4 h。吡格列酮组给予吡格列酮3 mg/(kg.d)灌胃1周,第8 d冠状动脉结扎前1 h再灌胃1次。对照组给予等量等渗盐水灌胃处理。T1组用于测量各组缺血再灌注后心肌梗死面积的变化。T2组用于观察各组再灌注4 h后血清中磷酸激酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平,并用凝胶电泳迁移率(EMSA)实验检测过氧化物增殖子激活受体-γ(PPAR-γ)、核因子-kappa B(NF-κB),用酶联免疫吸附实验(ELASA)检测心肌组织单核细胞趋化蛋白-1(MCP-1)的表达变化情况。使用光学显微镜观察心肌组织病理变化。结果:与对照组相比,①吡格列酮组心肌梗死面积明显降低(P<0.01),血清CK-MB、LDH水平下降明显(P<0.01),光镜观察心肌组织病理变化明显减轻;②应用吡格列酮后,能够增强缺血再灌注心肌PPAR-γ表达,而NF-κB、MCP-1表达明显降低(P<0.01)。结论:吡格列酮对心肌缺血再灌注损伤具有保护作用,且这种保护作用可能是通过激活PPAR-γ而抑制NF-κB表达,从而下调MCP-1表达实现的。
Objective： To investigate the protective effect of pioglitazone on myocardial ischemia-reperfusion injury and the action mechanism. Methods： Thirty-four rats with normal ECG graphs were randomly assigned to a T1 and a T2 group. The former was further divided into a control （ n = 5 ） and a pioglitazone group （ n = 5 ）, and the latter into a control （ n = 8 ） a sham operation （ n = 8 ） and a pioglitazone group （ n = 8）. The sham operation group underwent opening of the chest only without ligation of the coronary artery, and the other groups received a 30-minute ligation of the coronary artery and a 4-hour reperfusion. Pioglitazone was administered intragastrically to the pioglitazone group at the dose of 3 mg/kg·d-1 for 1 week, and saline was given to the control group at the same dose. The size of myocardial infarct was measured in the T1 group. In the T2 group, the levels of serum MB isoenzyme of crea- tine kinase （CK-MB） and lactate dehydrogenase （LDH） were measured 4 hours after reperfusion, the expressions of the peroxisome proliferator activated receptor-γ （PPAR-γ） and the nuclear factor kappa B （NF-κB） were determined by electrophoretic mobility-shift assay （EMSA）, and monocyte chemoattrac- tant protein-1 （MCP-1） in the ischemia-reperfusion myocardium was detected by enzyme linked immunosorbent assay （ELASA）. The histological changes in the myocardium were observed under the microscope. Results ： Compared with the control, the size of myocardial infarct was statistically smaller （P 〈 0.01 ） , the levels of serum CK-MB and LDH significantly decreased （P 〈 0.01 ） and the histopathological changes of the myocardium markedly lessened in the pioglitazone group. Pioglitazone increased the expression of PPAR-γ in the ischemia-reperfusion myocardium and significantly reduced the expressions of NF-κB and MCP-1 （P 〈 0.01 ）. Conclusion： Pioglitazone protects the myocardium against ischemia- reperfusion injury, which may be attributed to its down-regulation of the MCP-1 expression by activating PPAR-γ and inhibiting the expression of NF-κB.
出处
《医学研究生学报》
CAS
2008年第2期148-152,I0003,共6页
Journal of Medical Postgraduates
基金
南京军区医药卫生科研基金资助项目(批准号:06MA126)
关键词
缺血再灌注
吡格列酮
过氧化物增殖子激活受体
Ischemia-reperfusion
Pioglitazone
Peroxisome proliferators activated receptor
作者简介
刘晓军（1981-），男，山东青岛人，医学硕士研究生，从事心胸外科专业。
通讯作者：景华（1951-），男，江苏南通人，医学硕士，博士研究生导师，从事心胸外科专业。
