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首页> 外文期刊>The journal of sexual medicine >A protein tyrosine kinase inhibitor, imatinib mesylate (gleevec), improves erectile and vascular function secondary to a reduction of hyperglycemia in diabetic rats.
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A protein tyrosine kinase inhibitor, imatinib mesylate (gleevec), improves erectile and vascular function secondary to a reduction of hyperglycemia in diabetic rats.

机译：酪氨酸激酶蛋白抑制剂甲磺酸伊马替尼（gleevec）可改善糖尿病大鼠的高血糖症，从而改善勃起和血管功能。

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INTRODUCTION: Erectile dysfunction (ED) afflicts 50% of diabetic men, many of whom experience poor results with phosphodiesterase type 5 inhibitors. The protein tyrosine kinase (PTK) inhibitor imatinib (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) has therapeutic potential in diabetic men by maintaining beta-cell function. AIM: To determine if imatinib has a beneficial effect on erectile and vascular function in diabetic rats. METHODS: Male Sprague-Dawley rats were divided into six groups: (i) control; (ii) imatinib (50mg/kg, daily gavage)-treated control; (iii) diabetic; (iv) preventive imatinib (8 weeks); (v) reversal imatinib (4 weeks untreated diabetes and 4 weeks of treatment); and (vi) insulin (8 weeks)-treated diabetic rats. MAIN OUTCOME MEASURES: After 8 weeks, all groups underwent cavernosal nerve stimulation and measurements of intracavernosal pressure (ICP) and mean arterial pressure (MAP). Contractile and relaxation responses were evaluated using isolated strips of corpus cavernosum smooth muscle (CCSM) and aorta. RESULTS: Diabetic rats exhibited a 32% decrease in weight and fivefold increase in blood glucose levels. Imatinib-treated diabetic rats gained weight and partially improved blood glucose levels. Diabetic rats displayed a decrease in ICP/MAP. While maximum electrical field stimulation- and acetylcholine (ACh)-induced relaxations in CCSM strips from the diabetics were reduced, preventive imatinib or insulin treatment normalized ICP/MAP ratios and improved relaxation responses. ACh responses in diabetic aortas were diminished by 50.1% and restored by imatinib. While contractile responses to phenylephrine in diabetic CCSM were not altered, there was a significant enhancement (59.4 %) in the aortic contractile response in diabetic rats, which was restored by imatinib and insulin treatment. CONCLUSIONS: In diabetic rats, prolonged therapy with imatinib improves diabetes-related ED and vascular function, which may involve normalization of high glucose levels and restoration of PTK activation. Future studies are needed to elaborate on the actions of imatinib on diabetic vascular complications.
机译：简介：勃起功能障碍（ED）困扰着50％的糖尿病男性，其中许多人接受5型磷酸二酯酶抑制剂的治疗效果不佳。蛋白酪氨酸激酶（PTK）抑制剂伊马替尼（Gleevec，诺华制药，瑞士巴塞尔）通过维持β细胞功能在糖尿病男性中具有治疗潜力。目的：确定伊马替尼对糖尿病大鼠的勃起和血管功能是否有有益作用。方法：雄性Sprague-Dawley大鼠分为六组： （ii）伊马替尼（50mg / kg，每日管饲）治疗的对照组; （iii）糖尿病; （iv）预防性伊马替尼（8周）; （v）逆转伊马替尼（4周未经治疗的糖尿病和4周治疗）; （vi）用胰岛素（8周）治疗的糖尿病大鼠。主要观察指标：8周后，所有组均进行海绵体神经刺激并测量海绵体内压力（ICP）和平均动脉压（MAP）。使用离体的海绵体平滑肌（CCSM）和主动脉条评估收缩和松弛反应。结果：糖尿病大鼠的体重减轻了32％，血糖水平增加了五倍。伊马替尼治疗的糖尿病大鼠体重增加，血糖水平得到部分改善。糖尿病大鼠的ICP / MAP降低。尽管最大程度的电场刺激和乙酰胆碱（ACh）诱导的糖尿病患者CCSM试纸条的松弛减少，但预防性伊马替尼或胰岛素治疗使ICP / MAP比值正常化并改善了松弛反应。糖尿病主动脉中的ACh反应降低了50.1％，伊马替尼可恢复该反应。尽管在糖尿病CCSM中对苯肾上腺素的收缩反应没有改变，但糖尿病大鼠的主动脉收缩反应有显着增强（59.4％），通过伊马替尼和胰岛素治疗可以恢复。结论：在糖尿病大鼠中，伊马替尼的长期治疗可改善糖尿病相关的ED和血管功能，这可能涉及高血糖水平的正常化和PTK活化的恢复。需要进一步研究以阐明伊马替尼对糖尿病血管并发症的作用。

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