南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (09): 1359-1362.

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伊贝沙坦对糖尿病大鼠心脏一氧化氮系统的影响

钱孝贤； 陈燕铭； 吴伟康； 刘勇； 周彬； 刘金来； 陈璘；   

  1. 中山大学第三医院心血管内科； 中山大学中西医结合研究所 广东广州510080； 中山大学第三医院内分泌科； 中山大学心血管病研究所； 中山大学中西医结合研究所； 广东广州510080； 中山大学心血管病研究所广东广州510080； 广东广州510630； 广东广州5100803；
  • 出版日期:2006-09-20 发布日期:2006-09-20

Effects of irbesartan on nitric oxide system in the heart of diabetic rats

QIAN Xiao-xian1-3, CHEN Yan-ming4, WU Wei-kang2, 3, LIU Yong1, 2, ZHOU Bin1, 2, LIU Jin-lai1, 2, CHEN Lin1, 2 1Department of Cardiology, 4Department of Endocrinology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; 2Cardiovascular Institute, 3Institute for Integrated Traditional Chinese and Western Medicine, Sun Yat-sen University, Guangzhou 510080, China   

  1. 中山大学第三医院心血管内科； 中山大学中西医结合研究所 广东广州510080； 中山大学第三医院内分泌科； 中山大学心血管病研究所； 中山大学中西医结合研究所； 广东广州510080； 中山大学心血管病研究所广东广州510080； 广东广州510630； 广东广州5100803；
  • Online:2006-09-20 Published:2006-09-20

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摘要： 目的探讨血管紧张素Ⅱ受体拮抗剂伊贝沙坦对糖尿病大鼠心脏的保护作用及其一氧化氮(NO)机制。方法将30只Wistar大鼠随机分为对照组、糖尿病组和伊贝沙坦组3组,每组10只。大鼠腹腔一次注射2g/L链脲佐菌素(50mg/kg)造模,造模后12周终止实验处死大鼠,取血、尿和心脏标本,测定尿量、体质量、心脏质量/体质量的比值、血糖、糖化血红蛋白(HbA1c);测定血清和心脏组织NO的含量;并通过免疫组化观察心肌诱生型一氧化氮合酶(iNOS)的表达,RT-PCR检测iNOSmRNA的表达。结果12周终止实验时,糖尿病组和伊贝沙坦组大鼠的尿量、心脏质量/体质量比值、血糖、HbA1c、尿液、血清和心脏组织的NO水平均明显高于对照组,而体质量明显低于对照组(P<0.05);伊贝沙坦组大鼠的心脏质量/体质量比值、尿液、血清和心脏组织的NO水平明低于糖尿病组(P<0.05)。免疫组化发现伊贝沙坦组大鼠心脏组织的iNOS表达明显降低。RT-PCR发现伊贝沙坦组大鼠心脏组织的iNOSmRNA表达明显降低。结论NO和iNOS参加了糖尿病心肌病的发生,伊贝沙坦能抑制糖尿病大鼠心肌iNOS的基因和蛋白表达,减少NO产生。 

Abstract: Objective To investigate the effects of irbesartan for heart protection and on heart nitric oxide (NO) system in diabetic rats. Methods Thirty adult male Wistar rats were randomly divided into three equal groups, namely control group, diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the rats were sacrificed and the urine volume, body weight, ratio of heart to body weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO levels in the serum and myocardium were determined. Inducible nitric oxide synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA detected by RT-PCR. Results Urine volume, ratio of heart to body weight, plasma glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and irbesartan rats were significantly greater than those of normal controls (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and heart tissue in rats of irbesartan group were significantly decreased as compared with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression decreased significantly in irbesartan group, but not in diabetes group. Conclusions The abnormality in NO and iNOS mRNA expression might be related to diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein expressions and reduce NO levels in STZ-induced diabetic rats.

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