奥美沙坦对糖尿病大鼠腹主动脉球囊损伤后内膜增生及氧化应激的影响

Effects of olmesartan on hyperplasia of neointima and oxidative stress after abdominal aortas balloon injury in diabetic rats

目的:探讨奥美沙坦应用于糖尿病大鼠腹主动脉球囊损伤后对内膜厚度、超氧化物歧化酶(SOD)、丙二醛(MDA)含量和谷胱甘肽过氧化酶(GSH-PX)活力的的影响。方法:以SD雄性大鼠为研究对象,随机选取10只作为正常对照组(N组),余70只以链脲佐菌素(STZ)诱导建立糖尿病模型,将糖尿病大鼠随机分为糖尿病组(DM组)、糖尿病+球囊损伤假手术组(Sham组)、糖尿病+球囊损伤手术组(BI组)、糖尿病+球囊损伤手术+奥美沙坦治疗组(OM组)。5组大鼠均于术后第1天开始灌胃,OM组使用奥美沙坦,其余组用生理盐水,术后28 d取材,HE染色检测腹主动脉内膜厚度(I)、中膜厚度(M)和内膜与中膜的厚度比(I/M);试剂盒法检测血浆中SOD、MDA含量和GSH-PX活力。结果:HE染色结果示,与N组相比,DM组、Sham组血管内膜未见明显增生;与N组相比,OM组与BI组内膜可见明显增生(P<0.01);与OM组[(0.094±0.016)mm]相比,BI组内膜增生程度[(0.130±0.037)mm]较重(P<0.01)。与N组相比,其余4组SOD含量和GSH-PX活力均降低(P<0.01);与OM组比较,BI组SOD含量减少,GSH-PX活力降低(P<0.05)。与N组比较,其余4组MDA含量明显增加(P<0.01);与OM组比较,BI组MDA含量增加(P<0.01)。结论:奥美沙坦可以抑制糖尿病大鼠腹主动脉球囊损伤后再狭窄的发生,其机制可能与增加SOD含量和GSH-PX活力、减少MDA含量有关。

Objective： To explore the effects of olmesartan on hyperplasia of neointima,the content of superoxide dismutase（ SOD） and malondialdehyde（ MDA）,and glutathione peroxidase（ GSH-PX） enzyme activity after abdominal aortas balloon injury in streptozocin（ STZ） induced diabetic rats. Methods： Healthy adult male SD rats were randomly divided into two parts： normal control group（ N,n = 10）,seventy rats were used to establish diabetes models. The diabetic rats were randomly divided into four groups： diabetes group（ DM）,diabetes ＋balloon injury control group（ Sham）,diabetes ＋ balloon injury group（ BI）,diabetes ＋ balloon injury ＋ olmesartan group（ OM）. Five groups rats were gavaged daily after surgery. After 28 days,the rats were killed to detect the abdominal aorta intima thickness（ I）,tunica media thickness（ M） and the ratio of them（ I / M）. The plasma SOD,MDA content and GHS-PX enzyme activity were detected. Results： HE staining results showed,compared with group N,there was no obvious intima hyperplasia in group DM and Sham; and there was obvious intima hyperplasia in group OM and BI（ P〈0. 01）; compared with group OM,there was obvious intima hyperplasia in group BI（ P〈0. 01）. Compared with group N,the content of SOD and the GSH-PX enzymatic activity were reduced in the other four groups（ P〈0. 01）; Compared with group OM,the content of SOD and the GSH-PX enzymatic activity were decreased considerably in group BI（ P〈0. 05）. Compared with group N,the content of MDA were significantly increased in the other four groups（ P〈0. 01）; compared with group OM,the content of MDA increased considerably in group BI（ P〈0. 01）. Conclusion： Olmesartan can inhibit the vascular restenosis after abdominal aortas balloon injury in diabetic rats,probably by increasing the content of SOD and GSH-PX enzyme activity,and reducing the content of MDA.