依布硒啉和维生素E降血压及心脏保护作用  

The Protective Role of Ebselen and VitE on Hypertensive Heart Damage in NO-deficient Rats

作　　者：周斯平[1] 吴延庆[1] 程晓曙[1] 张诗渊[1] 

机构地区：[1]南昌大学第二附属医院心内科,江西南昌330006

出　　处：《中华高血压杂志》2008年第6期543-546,共4页Chinese Journal of Hypertension

摘　　要：背景持续给予大鼠一氧化氮合酶抑制剂(L-NAME)后,会出现血压升高、血管周围纤维化、心肌肥大、心肌坏死及纤维化等心血管重构及血管、心肌的炎症反应。以往研究提示心肌及血管局部组织中的肾素血管紧张素系统(RAS)参与了高血压及心血管重构的形成过程,这可能通过氧自由基(OFR)机制。目的观察抗氧化剂依布硒啉(Ebselen)、维生素 E(VitE)对 L-NAME所致一氧化氮(NO)缺乏性高血压大鼠心脏损害的防治作用。方法 Wistar 大鼠40只,随机分5组,每组8只,分为正常对照组(对照组,自由饮食及饮水,n=8)、实验对照组[实验组,L-NAME 50 mg/(kg·d),n=8]、Ebselen 组[Ebs 组,L-NAME 50 mg/(kg·d)+Ebs 30 mg/(kg·d),n=8]、VitE 组[L-NAME 50 mg/(kg·d)+VitE 40 mg/(kg·d),n=8]、Ebselen 和 VitE 联用组[联用组,给予 L-NAME50 mg/(kg·d)+Ebs 30 mg/(kg·d)+VitE 40 mg/(kg·d),n=8],灌胃法给药。隔周称重并测血压。8周末处死大鼠采集心脏组织标本及血液标本,测定血及心肌匀浆液中一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、超氧阴离子(O_2^-)的活性,测大鼠心脏质量/体质量及左室壁厚度。结果①实验组血压渐升高,到8周末比对照组明显增加(P<0.01),抗氧化剂组比实验组血压低(P<0.05),联用组血压显著低于 Ebs 组(P<0.01),Ebs 组低于 VitE 组(P<0.05)。②实验组血清、心脏组织 NO 水平、GSH-PX 均明显低于对照组(P<0.01),抗氧化剂组明显高于实验组(P<0.05),联用抗氧化剂组高于单用组(P<0.05),Ebs 组高于VitE 组(P<0.05)。③实验组血清及心脏组织中 O_2^-活性、MDA 活性、心脏组织中 AngⅡ活性、心脏质量/体质量及左室壁厚度明显大于正常,抗氧化剂组明显小于实验组(P<0.05),联用抗氧化剂组小于单用组,Ebs 组小于VitE 组(P<0.05)。血清中 AngⅡ活性各组间无明显差异。结论 Ebselen 和 VitE 对 NO 缺乏所致的高血压心脏损害具有保�Background Chronic administration with inhibitor of nitric oxide synthase （Nco-nitro-L-arginine methyl ester, L-NAME） induces persistent hypertension, cardiovascular remodeling, surrounding vascular fibrosis, necrosis and hypertrophy of myocardium, and inflammation in cardiovascular system. Local RAS involves in hyper- tension and remodeling of cardiovascular system, via increasing production of oxygen free radicals （OFR）. Objective To elucidate the preventive and therapeutic effect of antioxidant Ebselen and/or VitE on hypertensive heart damage in NO deficient rats induced by L-NAME. Methods Thirty-two Wistar rats were administered with L-NAME 50 mg/（kg·d） by garage for 8 weeks, and randomized to received a placebo（L） , or Ebs（S, 30 mg/kg·d） , or VitE（V, 40 mg/kg·d） or Ebs 30 mg/（kg·d）＋VitE 40 mg/（kg·d） , with 8 normal Wistar as control. Body mass and SBP were measured fortnightly. Plasma and homogenate of heart were collected for NO, AngⅡ, GSH-PX, MDA and O2 determination. Results Eight weeks after L-NAME administration, SBP in experimental groups was obviously higher than that of control （P〈0.01）. Antioxidants （Ebs or VitE） administered rats had lower SBP（P〈0.05） with combined Ebs and VitE produced lowest SBP. Ebs was shown to have greater antihy- pertensive effect than that by VitE（P〈0.05）. The NO level, the activity of GSH-PX in the serum and myocardium in experimental rats were obviously lower than those in normal Wistar rats. Combination treatment of Ebs and VitE was demonstrated to have most significant antioxidant effect than that either by Ebs or VitE monotherapy mani- festated by higher NO level, GSH-PX activities and lower MDA, O2-in serum and myocardium. Conclusion Combined Ebselen and VitE treatment was most affective in protection of heart damage from oxidative stress in the NO-deficient hypertensive rats.

关 键 词：氧自由基 高血压 心脏损害 一氧化氮 抗氧化剂 

分 类 号：R544.1[医药卫生—心血管疾病]