替米沙坦对球囊损伤后2型糖尿病大鼠颈动脉内膜增生及ACE2表达的影响  

Effect of telmisartan on carotid artery intimal hyperplasia after balloon catheter injury and ACE2 expression in the model of type 2 diabetes rats

作　　者：周明明[1] 陈明[1] 首云锋[1] 陈万[1] 

机构地区：[1]重庆医科大学附属第一医院心内科,重庆400016

出　　处：《中国医院药学杂志》2010年第6期460-464,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的:观察2型糖尿病大鼠颈动脉球囊导管损伤后血管内膜血管紧张素转化酶2(ACE2)的表达,初步探讨替米沙坦对球囊导管损伤后动脉内膜增生的作用及机制,血管ACE2表达的调节作用及对其的影响。方法:30只7周龄雄性SD大鼠高糖高脂饮食4周后腹腔注射链尿佐菌素(STZ,35mg·kg-1)建成2型糖尿病大鼠模型,将建成的模型经颈外动脉行球囊损伤成功后将大鼠分成4组,每组8只:正常对照组(NC)、2型糖尿病组、单纯球囊损伤组、替米沙坦组(0.8mg·kg-1.d-1)。药物治疗2周后,用RT-PCR法测定颈动脉中ACE2mRNA的表达水平,免疫组化法比较ACE2蛋白的表达。结果:与正常SD大鼠相比,2型糖尿病大鼠颈动脉内膜ACE2mRNA及其蛋白的表达均明显降低,分别降低30.1%,57.1%(P<0.05).与糖尿病模型组比较,替米沙坦组ACE2mRNA及蛋白水平增加(P<0.01),与单纯损伤组比较ACE2mRNA和蛋白的表达亦明显增加,分别增加44.0%和63.6%(P<0.01)。结论:(1)动脉内膜ACE2表达水平的降低可能是糖尿病大鼠动脉病变的发病机制之一;(2)ARB可能是通过增加动脉内膜局部ACE2的表达而发挥血管保护作用。OBJECTIVE To investigate angiotensin-converting enzyme 2 （ACE2） expression in the carotid artery intima of type 2 diabetes rats after balloon catheter injury, preliminary study of telmisartan on the artery after balloon catheter injury in the role of intimal hyperplasia and mechanism , vascular ACE2 expression and affect regulation. METHODS 30 7-week-old male Sprague-Dawley rats were maintained on the diet enriched with high glucose and high fat , for 4 weeks the rats received intraperitoneal injection of streptozotocin （STZ, 35 mg. kg-1 ）to produce type 2 diabetes rat model. The carotid artery of this model was denuded of the endothelium with a ball capsule through the external carotid artery. After this,the rats were divided into 4 groups of 8： normal control group （NC）, type 2 diabetes mellitus group, balloon injury alone group, telmisartan group （0. 8 mg-kg·d-1 ）. After 2 weeks of treatment, the expression level of ACE2mRNA in carotid artery was determined by RT- PCR, and compared the expression of ACE2 protein by immunohistochemistry. RESULTS Compared with the normal SD rats, carotid ACE2 mRNA and protein expression were significantly decreased in type 2 diabetes rat, respectively 30. 1%, 57. 1% （P〈0. 05）. Compared with diabetes mellitus model group, in telmisartan group ACE2 mRNA expression level increased（P〈 0. 01）,and compared with the simple injury group the ACE2 mRNA and protein expression also increased significantly, increased by 44.0 % and 63.6 %（P〈0. 01） . CONCLUSION （ 1 ） Lower expression level of ACE2 in artery intima may be one of the mechanisms which induces arterial disease in diabetic rats （2） ARB may play a role in vascular protection, partially through an increase in intima of ACE2 expression.

关 键 词：2型糖尿病大鼠 血管紧张素转化酶2 血管紧张素受体拮抗剂 动脉内膜增生 

分 类 号：R966[医药卫生—药理学]