摘要
目的观察糖尿病大鼠心肌缺血再灌注(MIR)时血管紧张素Ⅱ(AngⅡ)、醛固酮(aldosterone,ALD)、胰岛素样生长因子(IGF-1)、细胞间黏附分子-1(ICAM-1)和自由基代谢的变化及辛伐他汀对其的影响,探讨糖尿病大鼠MIR损伤的可能机制。方法制作糖尿病大鼠模型,造模成功后4周作MIR模型。糖尿病大鼠30只随机分为假手术对照组,MIR组和辛伐他汀治疗组。放射免疫法检测血浆AngⅡ、ALD和血清IGF-1水平,免疫组织化学法检测心肌ICAM-1蛋白表达。检测血清、心肌组织SOD、丙二醛和GSH-PX及心肌线粒体ATP酶活性。结果与假手术对照组相比,MIR组血浆AngⅡ、ALD明显升高,血清IGF-1含量明显降低;心肌线粒体Na+,K+-ATP酶、Mg++-ATP酶、Ca++-ATP酶活性明显下降;血清、心肌丙二醛明显升高,血清、心肌SOD和GSH-PX明显降低;心肌ICAM-1蛋白表达明显升高。用辛伐他汀后血浆AngⅡ、ALD低于MIR组,血清IGF-1水平高于MIR组;心肌线粒体Na+,K+-ATP酶、Mg++-ATP酶、Ca++-ATP酶活性高于MIR组;血清、心肌丙二醛低于MIR组,血清、心肌SOD和GSH-PX水平高于MIR组;心肌ICAM-1蛋白表达低于MIR组。结论糖尿病MIR时有大量ICAM-1蛋白表达及AngⅡ、ALD、IGF-1水平的变化,与心肌损伤关系密切。辛伐他汀可通过减少ICAM-1蛋白表达水平,减少AngⅡ、ALD,增加IGF-1水平起心肌保护作用。糖尿病MIR时自由基产生增多,辛伐他汀能加速自由基的清除,保护心肌组织免受氧化损伤。
[Objective] To observe the effects of Simvastatin on the changes of angiotensin Ⅱ （Ang Ⅱ ）,aldosterone（ALD）, insulin-like growth factor-1 （IGF-1）, the intercellular adhesion molecule-1 （ICAM-1）and free radicals in ischemic-reperfused myocardium of diabetic rats, and to investigate the pathogenesis of myocardial ischemic reperfusion injury in diabetic rats. [Methods] The diabetic rat model was established by streptozotocin xnjection into abdominal cavities of Spraque-Dawley rats. Four weeks later, the myocardial ischemic-reperfused models were established in anesthetic SD rats. Thirty diabetic SD rats were randomly divided into three groups with 10 rats in each group （sham group, MIR group and Simvastatin group）. The changes of plasma Ang Ⅱ, ALD and serum IGF-1 were examined with RIA. ICAM-1 protein expression was determined with immunohistochemical method. The quantity of malonialdehyde（MDA） in serum and myocardial tissues were tested. The activities of superoxide dismutase（SOD） and glutathione peroxidase（GSH-PX） in serum and myocardial tissues were measured. The activities of Na^＋, K^＋-ATPase, Mg^＋＋-ATPase,Ca^＋＋-ATPase in myocardial mitochondria were measured. [Results] Compared with sham group, the levels of Ang Ⅱ and ALD in plasma were increased significantly, the level of serum IGF-1 was decreased significantly in MIR group. Compared with MIR group, the levels of Ang Ⅱ and ALD in plasma were decreased significantly, the levels of IGF-1 were increased significantly in Simvastatin group. Compared with sham , the activities of Na^＋, K^＋-ATPase, Mg^＋＋-ATPase, Ca^＋＋-ATPase in myocardial mitochondria were decreased significantly in MIR group.Compared with MIR groups, the activities of Na^＋, K^＋-ATPase, Mg^＋＋-ATPase, Ca^＋＋-ATPase in myocardial mitochondria were increased significantly in Simvastatin group. Compared with sham group, the quantity of in MDA in serum and myocardium was increased significantly, the levels of SOD and GSH-PX in s
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2008年第12期1663-1667,共5页
China Journal of Modern Medicine
关键词
心肌缺血再灌注
糖尿病
辛伐他汀
细胞间黏附分子-1
自由基
myocardial ischemic reperfusion
diabetes
Simvastatin
intercellular adhesion molecule-l
free radicals
