Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix
Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix
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DOI：
10.1152/ajpheart.00027.2008
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发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Chitaley, Kanchan
中科院分区：
文献类型：
--
作者：
Luttrell, Ian P.;Swee, Mei;Chitaley, Kanchan
患有 II 型糖尿病相关勃起功能障碍 (ED) 的男性人数持续快速增长；然而，大多数基础科学研究都在 I 型糖尿病动物模型中研究了 ED 的机制。在本研究中，我们首先使用瘦素受体突变的 db/db 和野生型对照 BKS 小鼠建立 II 型糖尿病 ED 体内小鼠模型。此外，我们假设双重机制损伤导致 II 型糖尿病小鼠的勃起功能受损、血管反应性改变和静脉闭塞障碍。体内勃起功能通过电刺激海绵体神经后将海绵体内压（ICP）标准化为平均动脉压（MAP）来测量。通过体内盐水输注后维持体内ICP升高来评估静脉闭塞。通过肌动描记法在体外检查分离的海绵体对收缩和扩张刺激的血管反应性。分别通过羟脯氨酸和锁链素的定量，以及通过定量PCR和分离海绵体的组织学分析来评估胶原蛋白和弹性蛋白含量。与 BKS 小鼠相比，db/db 小鼠的勃起功能显着下降，其方式与静脉闭塞能力受损和流入减少一致。与 BKS 小鼠相比，db/db 小鼠的海绵体血管收缩增强，扩张减弱，表明松弛能力总体降低，从而损害了海绵体空间的填充。检测到锁链素和羟脯氨酸减少，原弹性蛋白、原纤维蛋白-1 和 α 1(I) 胶原蛋白 mRNA 水平降低。这些血管反应性和正弦曲线基质的改变可能会改变组织顺应性的可分配性，从而阻止勃起所需的正常扩张。
The number of men with type II diabetes-associated erectile dysfunction (ED) continues to grow rapidly; however, the majority of basic science studies has examined mechanisms of ED in animal models of type I diabetes. In this study, we first establish an in vivo mouse model of type II diabetic ED using the leptin receptor mutated db/db and wild-type control BKS mouse. Furthermore, we hypothesized that dual mechanistic impairments contribute to the impaired erectile function in the type II diabetic mouse, altered vasoreactivity, and venoocclusive disorder. In vivo erectile function was measured as intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP) following electrical stimulation of the cavernosal nerve. Venoocclusion was assessed by the maintenance of elevated in vivo ICP following intracorporal saline infusion. Vasoreactivity of isolated cavernosum in response to contractile and dilatory stimulation was examined in vitro by myography. Collagen and elastin content were evaluated by quantification of hydroxyproline and desmosine, respectively, as well as by quantitative PCR and histological analysis of isolated cavernosum. Erectile function was significantly decreased in db/db vs. BKS mice in a manner consistent with impairments in venoocclusive ability and decreased inflow. Heightened vasoconstriction and attenuated dilation in cavernosum of db/db vs. BKS mice suggest an overall lowered relaxation ability and thus impaired filling of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as lowered mRNA levels for tropoelastin, fibrillin-1, and alpha 1(I) collagen were detected. These vasoreactive and sinusoidal matrix alterations may alter tissue compliance dispensability, preventing the normal expansion necessary for erection.