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在糖尿病大鼠模型中,在常规胰岛素治疗基础上加用辛伐他汀可维持对5型磷酸二酯酶抑制剂的勃起反应。

Erectile response to type 5 phosphodiesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetes.

作者信息

Park K, Cho S Y, Kim S W

机构信息

Department of Urology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Int J Androl. 2011 Oct;34(5 Pt 2):e468-74. doi: 10.1111/j.1365-2605.2011.01196.x. Epub 2011 Jul 26.

DOI:10.1111/j.1365-2605.2011.01196.x
PMID:21790657
Abstract

Enhanced RhoA/Rho-kinase pathway plays anti-erectile role and is associated with reduced response to type 5 phosphodiesterase inhibitor (PDE5I) in diabetic animals. We tested whether adjunctive simvastatin to conventional insulin treatment would restore PDE5I-induced as well as basal erectile response in diabetic rat model of erectile dysfunction. Forty 8-week-old male Sprague-Dawley rats were equally divided into four groups, (n=10) i.e. the diabetic group (D), age-matched control (C), conventional insulin treatment (I) and adjunctive simvastatin to conventional insulin treatment (S). Following 10weeks of intraperitoneal injection of streptozotocin (STZ, 35mg/kg), the group I and S received insulin (10U NPH/day) for 4weeks. Concurrently, group S received simvastatin (20mg/kg/day). Following 14weeks of diabetes induction, basal and PDE5I (intravenous mirodenafil 1mg/kg)-elicited erectile response were assessed during cavernous nerve electrostimulation. Then, penile tissues were processed for molecular assessment. Although group I failed to restore basal and PDE5I-induced erectile response, group S showed normalized erectile responses. Furthermore, group I showed improvement of only eNOS-related pathway, whereas group S effectively controlled both eNOS-related and RhoA/Rho-kinase pathway. Conclusively, adjunctive use of simvastatin to conventional insulin treatment showed more effectiveness in restoring erectile responses of diabetic rats by controlling the RhoA/Rho-kinase pathway than conventional insulin treatment alone.

摘要

增强的RhoA/ Rho激酶信号通路发挥抗勃起作用,并与糖尿病动物对5型磷酸二酯酶抑制剂(PDE5I)反应降低有关。我们测试了在传统胰岛素治疗基础上加用辛伐他汀是否能恢复糖尿病性勃起功能障碍大鼠模型中PDE5I诱导的以及基础勃起反应。40只8周龄雄性Sprague-Dawley大鼠平均分为四组,(n = 10)即糖尿病组(D)、年龄匹配对照组(C)、传统胰岛素治疗组(I)和在传统胰岛素治疗基础上加用辛伐他汀组(S)。腹腔注射链脲佐菌素(STZ,35mg/kg)10周后,I组和S组接受胰岛素(10U NPH/天)治疗4周。同时,S组接受辛伐他汀(20mg/kg/天)治疗。在诱导糖尿病14周后,在海绵体神经电刺激期间评估基础和PDE5I(静脉注射米罗地尔1mg/kg)诱导的勃起反应。然后,对阴茎组织进行分子评估。虽然I组未能恢复基础和PDE5I诱导的勃起反应,但S组的勃起反应恢复正常。此外,I组仅显示eNOS相关信号通路有所改善,而S组有效控制了eNOS相关和RhoA/ Rho激酶信号通路。总之,在传统胰岛素治疗基础上加用辛伐他汀比单独使用传统胰岛素治疗在通过控制RhoA/ Rho激酶信号通路恢复糖尿病大鼠勃起反应方面更有效。

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