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人组织激肽释放酶基因对2型糖尿病大鼠血压的影响及机制
引用本文:袁刚,王涛,赵春霞,肖啸,汪道文. 人组织激肽释放酶基因对2型糖尿病大鼠血压的影响及机制[J]. 中国病理生理杂志, 2006, 22(7): 1289-1294. DOI: 1000-4718
作者姓名:袁刚  王涛  赵春霞  肖啸  汪道文
作者单位:1华中科技大学同济医学院同济医院内科, 湖北 武汉 430030;2 美国Pittsburgh大学,Pittsburgh, PA 15261, USA
基金项目:国家863高技术研究发展计划资助项目(No.2001AA217121),国家自然科学基金资助项目(No.30470824)
摘    要:目的:探讨人组织激肽释放酶(HK)基因对2型糖尿病大鼠血压的影响及其机制。方法:高脂高糖饮食加小剂量链脲佐菌素建立2型糖尿病动物模型。以重组腺相关病毒为载体介导HK基因(HK组)或对照基因LacZ(LacZ组)在糖尿病大鼠体内表达,观察实验动物血压变化及离体主动脉对乙酰胆碱(Ach)依赖性血管舒张反应和一氧化氮(NO)、内皮素-1(ET-1)、内皮素受体A(ETA-R)表达。 结果:(1) HK组第2周开始出现血压下降,并一直持续到实验结束(12周时),而LacZ组血压无明显下降。(2) LacZ组离体主动脉对乙酰胆碱(Ach)依赖性血管舒张反应明显低于HK组。(3) HK组大鼠主动脉NO2-/NO3-浓度明显高于LacZ组,而ET-1和ETA-R mRNA明显低于LacZ组。 结论:重组腺相关病毒介导HK基因表达明显降低2型糖尿病大鼠血压,改善内皮依赖性血管舒张功能,原因可能与增加动脉NO释放,减少ET-1和ETA-R的表达有关。

关 键 词:糖尿病  组织激肽释放酶类  高血压  内皮依赖性血管舒张  一氧化氮  内皮缩血管肽1  
文章编号:1000-4718(2006)07-1289-06
收稿时间:2004-10-27
修稿时间:2004-10-272005-01-10

Effect of tissue kallikrein gene treatment on blood pressure in type 2 diabetic rats and its mechanism
YUAN Gang,WANG Tao,ZHAO Chun-xia,XIAO Xiao,WANG Dao-wen. Effect of tissue kallikrein gene treatment on blood pressure in type 2 diabetic rats and its mechanism[J]. Chinese Journal of Pathophysiology, 2006, 22(7): 1289-1294. DOI: 1000-4718
Authors:YUAN Gang  WANG Tao  ZHAO Chun-xia  XIAO Xiao  WANG Dao-wen
Affiliation:1Department of Internal Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China;2 University of Pittsburgh, Pittsburgh, PA 15261, USA
Abstract:AIM:To study the effect of tissue kallikrein gene (HK) treatment on blood pressure in type 2 diabetic rats and its mechanism. METHODS:Male Wistar rats were injected with low dose streptozotocin and fed with diets enriched in fat and sugar to form type 2 diabetic model. Recombinant adeno-associated viral vectors (rAAV)-mediated HK gene (HK group) or LacZ gene (LacZ group) was introduced to the diabetic rats. The systolic blood pressure was measured every 2 weeks. The acetylcholine (Ach)-dependent vasodilation response, the synthesis of nitric oxide (NO), the expression of endothelin-1 (ET-1) and endothelin-A receptor (ETA-R) in the aorta were detected. RESULTS:(1) Systolic blood pressure was significantly higher in diabetic rats than that in normal control rats. In HK group, systolic blood pressure was significantly reduced within 2 weeks after injection with rAAV·HK, reached near normal levels at 4 weeks and kept until the experiments ended (16 weeks). (2) In LacZ group, Ach-dependent vasodilation response of isolated aorta was markedly decreased than that in HK group (P<0.01). (3) The concentration of NO in the aorta of HK group were significantly higher than those in LacZ group. The expression of ET-1 and ETA-R mRNA were significantly decreased in HK group compared with those in LacZ group (P<0.01). CONCLUSION:rAAV-mediated HK gene delivery efficiently lowed blood pressure and attenuated the endothelial function partly through increasing the concentration of NO and inhibiting the expression of ET-1 and ETA-R of aorta in type 2 diabetic rats.
Keywords:Diabetes mellitus  Tissue kallikreins  Hypertension  Endothelium-dependent vasodilation  Nitric oxide  Endothelin-1  
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