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目的研究PPAR-γ激动剂罗格列酮对大鼠急性心肌梗死(acute myocardial infarction,AMI)后血管新生及内皮型一氧化氮合酶(endoth elial nitric oxide synthase,eNOS)表达调控的影响。方法健康成年SD大鼠60只,用随机数字表法分为假手术组、对照组、罗格列酮组、罗格列酮+L-NAME(NOS抑制剂)组、L-NAME组,每组12只。结扎大鼠冠状动脉左前降支建立急性心肌梗死动物模型。灌胃给予罗格列酮(3mg·kg-1·d-1)2周,同时腹腔内注射给予L-NAME(40mg·kg-1·d-1)2周。检测梗死周围缺血区CD31阳性染色血管数;以Westernblot及RT-PCR检测缺血区丝氨酸1177磷酸化内皮型一氧化氮合酶(phosphorylized endothelial nitric oxide synthase at Ser1177,p-eNOSSer1177)蛋白及eNOSmRNA的表达。结果①与对照组比较,罗格列酮组心肌梗死后CD31阳性染色血管数显著增加(P<0.05),而NOS抑制剂L-NAME则抑制了罗格列酮的这一作用。②罗格列酮组eNOSmRNA表达与对照组比较差异无统计学意义(P>0.05),而p-eNOSSer1177蛋白水平显著升高(P<0.05)。结论罗格列酮能促进大鼠急性心肌梗死后血管新生,其机制可能与其促进eNOS的磷酸化,从而介导内皮源性一氧化氮(endothelium-derived nitric oxide,EDNO)合成增加有关。
Objective To investigate the effects of PPAR-γ agonist rosiglitazone on angiogenesis and the expression of eNOS in rats after acute myocardial infarction (AMI). Methods Sixty healthy SD rats were randomly divided into sham operation group, control group, rosiglitazone group, rosiglitazone + L-NAME (NOS inhibitor) group and L-NAME group Group of 12. Animal models of acute myocardial infarction were established by ligation of left anterior descending coronary artery in rats. Rosiglitazone (3 mg · kg-1 · d-1) was given intragastrically for 2 weeks and L-NAME (40 mg · kg-1 · d-1) was intraperitoneally injected for 2 weeks. The number of CD31-positive blood vessels in ischemic zone of infarcted area was detected. The protein and eNOS mRNA of phosphorylized endothelial nitric oxide synthase at Ser1177 (p-eNOSSer1177) was detected by Western blot and RT-PCR expression. Results ① Compared with the control group, the number of CD31-positive vessels in the rosiglitazone group increased significantly (P <0.05), while the NOS inhibitor L-NAME inhibited the rosiglitazone effect. ② The expression of eNOS mRNA in rosiglitazone group was not significantly different from that in control group (P> 0.05), while the protein level of p-eNOSSer1177 was significantly increased (P <0.05). Conclusions Rosiglitazone can promote angiogenesis after acute myocardial infarction in rats, and its mechanism may be related to the promotion of eNOS phosphorylation and the increase of endothelium-derived nitric oxide (EDNO) synthesis.