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果糖和链脲佐菌素诱导的糖尿病大鼠主动脉和海绵体中 caveolin-1 表达和血管反应性的变化。

Changes in caveolin-1 expression and vasoreactivity in the aorta and corpus cavernosum of fructose and streptozotocin-induced diabetic rats.

机构信息

Department of Pharmacology, School of Pharmacy, Marmara University, Tibbiye St. 49 Haydarpaşa, Istanbul 34688, Turkey.

出版信息

Eur J Pharmacol. 2010 Sep 10;642(1-3):113-20. doi: 10.1016/j.ejphar.2010.05.049. Epub 2010 Jun 8.

Abstract

Hyperglycemia is a common defining feature in the development of endothelial dysfunction which plays a key role in the pathogenesis of both type 1 and type 2 diabetes. Caveolin-1 is the main structural component of caveolae which might be involved in the pathophysiology of macrovascular complications of diabetes. In this study we aimed to observe the effect of caveolin-1 on functional responses of aorta and corpus cavernosum in the streptozotocin and fructose-induced diabetes groups. Type 1 diabetes was induced by intraperitoneal administration of streptozotocin (60 mg/kg),. Type 2 diabetes by adding fructose in the rat's drinking water (10% (w/v)) for 8 weeks. For insulin treatment; rats were treated with insulin (6 U/kg) for 8 weeks. In Type I and Type II diabetic groups the contractile responses of corpus cavernosum strips to phenylephrine (EC(50):1.82 x 10(-5)M;1.47 x 10(-5)M, respectively)and relaxation responses to acetylcholine (EC(50):7.5 x 10(-5)M;4.48 x 10(-5)M, respectively)were significantly impaired. Contractile responses of aorticstrips to phenylephrine in diabetic groups were markedly decreased (EC(50):3.7.10(-7)M;2.61.10(-7)M respectively) and dose-dependent relaxation responses to acetylcholine were also attenuated (EC(50):3.23.10(-6)M; 2.0.10(-6)M respectively). Treatment with insulin improved the functional responses in the aorta and corpus cavernosum. Protein expression of caveolin-1 was increased in the aorta and corpus cavernosum of the diabetic groups, but this increase seen in the streptozotocin group was more significant than the fructose group. Our findings indicate that an attenuation of the functional responses in both diabetes groups were probably associated with an enhanced expression of caveolin-1, and therefore a decrease in the eNOS activity with a concomitant decrease in NO synthesis.

摘要

高血糖是内皮功能障碍发展的常见特征,在 1 型和 2 型糖尿病的发病机制中起着关键作用。窖蛋白-1 是小窝的主要结构成分,可能参与糖尿病大血管并发症的病理生理过程。在这项研究中,我们旨在观察窖蛋白-1 对链脲佐菌素和果糖诱导的糖尿病组主动脉和阴茎海绵体功能反应的影响。1 型糖尿病通过腹腔内给予链脲佐菌素(60mg/kg)诱导,2 型糖尿病通过在大鼠饮用水中添加果糖(10%(w/v))8 周诱导。胰岛素治疗;8 周给予胰岛素(6U/kg)治疗。在 1 型和 2 型糖尿病组中,阴茎海绵体条对苯肾上腺素(EC(50):1.82×10(-5)M;1.47×10(-5)M)的收缩反应和对乙酰胆碱(EC(50):7.5×10(-5)M;4.48×10(-5)M)的松弛反应明显受损。糖尿病组主动脉条对苯肾上腺素的收缩反应明显降低(EC(50):3.7.10(-7)M;2.61.10(-7)M),对乙酰胆碱的浓度依赖性松弛反应也减弱(EC(50):3.23.10(-6)M;2.0.10(-6)M)。胰岛素治疗改善了主动脉和阴茎海绵体的功能反应。糖尿病组主动脉和阴茎海绵体的窖蛋白-1 蛋白表达增加,但链脲佐菌素组的增加比果糖组更为显著。我们的研究结果表明,两组糖尿病患者的功能反应减弱可能与窖蛋白-1表达增强有关,从而导致 eNOS 活性降低,NO 合成减少。

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