罗格列酮对糖尿病小鼠急性心肌缺血的保护作用  

Protective effects of rosiglitazone on myocardial ischemia in diabetic mice

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作  者:项学军[1] 张亭亭[2] 洪浩[2] 

机构地区:[1]安徽医科大学附属安庆医院心血管内科,安庆246003 [2]中国药科大学药理教研室,南京210009

出  处:《安徽医科大学学报》2011年第10期1032-1035,共4页Acta Universitatis Medicinalis Anhui

摘  要:目的研究过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对糖尿病小鼠急性心肌缺血损伤的保护作用。方法小鼠尾静脉注射链脲霉素(STZ)150mg/kg诱导1型糖尿病模型,糖尿病小鼠分为4组,即糖尿病对照组、糖尿病心肌缺血组、罗格列酮高剂量组(3.2 mg/kg/d)及罗格列酮低剂量组(1.6 mg/kg/d),并设正常对照组。每组动物8只,灌胃给药,1周后连续2 d以背部皮下多点注射异丙肾上腺素20 mg/kg诱导急性心肌缺血模型,检测心电图、血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、心肌超氧化物岐化酶(SOD)及心肌组织病理,并测定血糖和血清胰岛素水平。结果与糖尿病心肌缺血组相比,罗格列酮高剂量和低剂量组小鼠心电图ST段显著下降,血清CK和LDH水平显著降低,心肌组织变性坏死明显减轻,SOD水平显著升高。但罗格列酮糖尿病小鼠血糖和血清胰岛素水平均无明显影响。结论罗格列酮可以显著改善糖尿病心肌缺血损伤,其作用机制可能与提高心肌SOD水平有关。Objective To investigate the protective effect of PPARγ agonist rosiglitazone on acute myocardial ischemia injury in diabetic mice.Methods Caudal vein injection of streptozotocin(STZ)(150 mg/kg)was used to induce type 1 diabetes model(DM)in mice,then the diabetic mice were randomly divided into four groups,the DM group,diabetic-myocardial ischemia(DMI) group,mice in DMI group were treated with high dose 3.2 mg/(kg·d)and low dose 1.6 mg/(kg·d) of rosiglitazone,accompanying with age-matched control mice.Acute myocardial ischemia injury was induced with subcutaneous injection of isoprenaline(ISO)(20 mg/kg) at the back for two days after administration of the diabetic mice with rosiglitazone for one week.The electrocardiograms were analyzed,the activities of LDH and CK in serum as well as the SOD activity in the myocardial tissue were assayed.Pathological slides of myocardium from the groups were also examined,and the fasting serum glucose(FSG) and insulin were determined.Results Compared with the DMI control mice,the mice administrated with high dose and low dose of rosiglitazone showed significant lower ECG-ST segments,and significant amelioration of the tissue degeneration of myocardial tissue observed by light microscope.In addition,the levels of serum CK and LDH in the DMI mice pretreated with rosiglitazone were significantly decreased,and the activities of myocardial SOD were significantly elevated.However,rosiglitazone had no significant influence on the blood glucose and serum insulin levels in the DMI mice.Conclusion Rosiglitazone significantly improve the myocardial ischemia injury in diabetic mice,which is involved in the elevation of the SOD activity in the myocardial tissue.

关 键 词:罗格列酮 糖尿病 心肌缺血 肌酸激酶 

分 类 号:R542.22[医药卫生—心血管疾病]

 

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