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2-溴乙胺抑制氨基脲敏感性胺氧化酶活性对糖尿病大鼠血管内皮的保护作用

王振花, 李潮生, 杨大浩, 徐峥嵘, 蔡军红, 陈军

广东医学院研究生学院，湛江 524000；深圳市宝安人民医院心血管内科，深圳 518100

摘要

本研究旨在观察糖尿病大鼠主动脉氨基脲敏感性胺氧化酶(semicarbazide-sensitive amine oxidase, SSAO)的活性变化，探讨2-溴乙胺(2-bromoethylamine, 2-BEA)抑制SSAO活性对糖尿病大鼠血管内皮的保护作用。制备大鼠主动脉组织匀浆作为SSAO来源，体外应用苯甲胺作为SSAO催化底物，检测不同浓度2-BEA对主动脉SSAO活性的抑制作用。采用链脲佐菌素(streptozotocin, STZ)单次腹腔注射诱导1型糖尿病大鼠模型，将成年Sprague Dawley (SD)大鼠随机分为正常对照(NC)组、糖尿病模型(DM)组、2-BEA 5 mg/kg组、2-BEA 20 mg/kg组，每组10只，2-BEA每天腹腔注射给药，连续8周。8周末，腹主动脉采血，硝酸还原酶法测定血浆一氧化氮(nitric oxide, NO)含量，放射免疫分析法测定血浆内皮素-1 (endothelin-1, ET-1)浓度，高效液相色谱法测定大鼠主动脉SSAO活性，观察主动脉形态及超微结构变化。结果显示，与NC组比，DM组大鼠主动脉SSAO活性、血浆ET-1浓度显著升高(P < 0.01)，而血浆NO含量显著降低(P < 0.01)；2-BEA抑制糖尿病大鼠主动脉SSAO活性，降低了血浆ET-1浓度并升高了血浆NO含量(P < 0.01)，2-BEA 20 mg/kg组效果比5 mg/kg组更明显(P < 0.05)，2-BEA组大鼠主动脉内皮损伤较DM组明显减轻。以上结果表明，2-BEA通过抑制主动脉SSAO活性保护糖尿病大鼠血管内皮。

关键词： 2-溴乙胺; 氨基脲敏感性胺氧化酶; 甲醛; 糖尿病; 内皮细胞

分类号：R363

[2-Bromoethylamine protects vascular endothelium by inhibiting SSAO activity in diabetic rats.] [Article in Chinese]

WANG Zhen-Hua, LI Chao-Sheng, YANG Da-Hao, XU Zheng-Rong, CAI Jun-Hong, CHEN Jun

Institute of Graduate, Guangdong Medical College, Zhanjiang 524000, China； Cardiovascular Department, Shenzhen Bao’an People’s Hospital, Shenzhen 518100, China

Abstract

The purpose of this study was to investigate the change of aortic semicarbazide-sensitive amine oxidase (SSAO) activity in diabetic rats and examine the effect of 2-bromoethylamine (2-BEA) on SSAO activity and vascular endothelium in diabetic rats. SSAO was prepared from rat aorta. For assessment of the inhibitory effect, the enzymes were preincubated in the presence of different concentrations of 2-BEA before the addition of benzylamine in vitro. Type 1 diabetic rat model was induced by a single intraperitoneal injection of streptozotocin (STZ). Sprague Dawley (SD) rats were randomly divided into normal control group (NC), diabetic model group (DM), 2-BEA 5 mg/kg group, 2-BEA 20 mg/kg group (n = 10 in each group). 2-BEA was administered daily via intraperitoneal injection for 8 weeks. At the end of 8 weeks, blood sample was collected from the abdominal aorta. Plasma nitric oxide (NO) was determined by nitrate reductase method. Plasma endothelin-1 (ET-1) was determined by radioimmunoassay. Aorta SSAO was determined by high performance liquid chromatography. The aorta was prepared to observe morphological changes and ultramicroscopic structures. The results were as follows: Compared with NC group, aortic SSAO activity and the plasma ET-1 were significantly increased (P < 0.01), and plasma NO was significantly decreased (P < 0.01) in DM group. 2-BEA decreased plasma ET-1 and elevated plasma NO by inhibiting aortic SSAO activity in diabetic rats (P < 0.01), and 2-BEA 20 mg/kg group was more significant than 2-BEA 5 mg/kg group (P < 0.05). Endothelial injury of 2-BEA group rats was less serious than DM group. These results suggest that 2-BEA protect aortic endothelium by inhibiting aortic SSAO activity.

Key words: 2-bromoethylamine; semicarbazide-sensitive amine oxidase; formaldehyde; diabetes; endothelium

收稿日期：2013-12-21　　录用日期：2014-02-10

通讯作者：陈军　　E-mail: 896860112@qq.com

引用本文：

王振花, 李潮生, 杨大浩, 徐峥嵘, 蔡军红, 陈军. 2-溴乙胺抑制氨基脲敏感性胺氧化酶活性对糖尿病大鼠血管内皮的保护作用[J]. 生理学报 2014; 66 (4): 476-482.

WANG Zhen-Hua, LI Chao-Sheng, YANG Da-Hao, XU Zheng-Rong, CAI Jun-Hong, CHEN Jun. [2-Bromoethylamine protects vascular endothelium by inhibiting SSAO activity in diabetic rats.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (4): 476-482 (in Chinese with English abstract).