福辛普利、替米沙坦单用或联用对糖尿病模型大鼠颈动脉内膜球囊损伤后血管紧张素转换酶2的影响研究

目的:考察福辛普利、替米沙坦单用或联用对糖尿病模型大鼠颈动脉内膜球囊损伤后血管紧张素转换酶2(ACE2)的影响及其作用机制。方法:取大鼠36只,均分为正常对照组、糖尿病模型组(蒸馏水)、球囊损伤组(蒸馏水)、福辛普利组(10mg·kg-1·d-1)、替米沙坦组(0.8mg·kg-1·d-1)和联用组(福辛普利10mg·kg-1·d-1、替米沙坦0.8mg·kg-1·d-1),每组6只,除正常对照组外,其余各组大鼠腹腔注射链脲佐菌素(35mg·kg-1)建立2型糖尿病模型。建模成功后,除糖尿病模型组外,其余各组大鼠行颈动脉内膜球囊损伤手术,手术前、后分别灌服给予相应药物1、2周,正常对照组相同时间给予蒸馏水,检测各组大鼠颈动脉中ACE2mRNA及其蛋白表达。结果:与正常对照组比较,球囊损伤组大鼠ACE2 mRNA及其蛋白表达均明显降低(P<0.05);与球囊损伤组比较,福辛普利组大鼠ACE2 mRNA及其蛋白表达没有明显差异(P>0.05),替米沙坦组和联用组大鼠ACE2mRNA及其蛋白表达明显增加(P<0.05),但2组间无显著差异(P>0.05)。结论:福辛普利并不能促进替米沙坦增强ACE2的表达;替米沙坦可能是通过增加动脉内膜局部ACE2的表达来发挥血管保护作用。

Effect of Fosinopril and Telmisartan Alone or in Combination on ACE2 after Carotid Intimal Balloon Injury in Type 2 Diabetes Rats

OBJECTIVE： To investigate the effect of telmisartan and fosinopril alone or in combination on the expression of angiotensin-converting enzyme 2 （ACE2） after carotid intimal balloon injury in type 2 diabetes rats.METHODS： 36 Male Sprague-Dawley rats were divided into normal control group,diabetes model group （distilled water）,balloon injury group （distilled water）,fosinopril group （10 mg·kg-1·d-1）,telmisartan group （0.8 mg·kg-1·d-1） and combined therapy group （fosinopril 10 mg·kg-1·d-1 and telmisartan 0.8 mg·kg-1·d-1） with 6 rats in each group.Except normal control group,above groups were given intraperitoneal injection of streptozotocin （STZ,35 mg·kg-1） to establish type 2 diabetes model.After modeling,those groups received carotid intimal balloon injury surgery except diabetes model group and were given relevant drugs for 1 and 2 weeks before and after surgery.At that time,normal control group was given stilled water.The expression level of ACE2 mRNA and ACE2 protein in carotid artery were determined.RESULTS： Compared with normal control group,the expression level of ACE2 mRNA and ACE2 protein in balloon injury group were decreased significantly （P0.05）.There was no significant difference in the expression level of ACE2 mRNA and ACE2 protein between balloon injury group and fosinopril group （P0.05）.The expression level of ACE2 mRNA and ACE2 protein in telmisartan group and combined therapy group were increased significantly （P0.05）,but no stastical difference between each other （P0.05）.CONCLUSIONS： Fosinopril can not promote the expression of ACE2 induced by telmisartan.Telmisartan can protect carotid artery by enhancing the expression of arterial intimal ACE2.