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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。
The purpose of this study was to investigate the changes of semicarbazide-sensitive amine oxidase (SSAO) in aortas of diabetic rats and to investigate the effect of 2-bromoethylamine (2-BEA) Protective effect of rat vascular endothelium. Aortic tissue homogenates from rats were used as the source of SSAO. Benzylamine was used as the substrate of SSAO in vitro to detect the inhibitory effect of 2-BEA on the activity of aortic SSAO. The adult Sprague Dawley (SD) rats were randomly divided into normal control (NC) group, diabetic model group (DM), and diabetic nephropathy group (DM). The diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) BEA 5 mg / kg group, 2-BEA 20 mg / kg group, 10 rats in each group. 2-BEA was administered intraperitoneally for 8 weeks. At the end of the 8th week, blood samples were taken from abdominal aorta, nitric oxide reductase (NO) levels were measured by enzyme-linked immunosorbent assay (ELISA), and the concentration of endothelin-1 (ET-1) Method to determine the activity of SSAO in rat aorta and observe the morphological and ultrastructural changes of the aorta. The results showed that compared with the NC group, the aortic SSAO activity and plasma ET-1 concentration in DM group were significantly increased (P <0.01), while the NO content in plasma was significantly lower (P <0.01); 2-BEA inhibited diabetic rats The activity of SSAO in aorta decreased plasma ET-1 concentration and increased plasma NO level (P <0.01), and the effect of 2-BEA 20 mg / kg group was more obvious than that of 5 mg / kg group BEA group rats aortic endothelial injury than DM group was significantly reduced. The above results show that 2-BEA protects the vascular endothelium of diabetic rats by inhibiting aortic SSAO activity.