National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
J Sex Med. 2009 Dec;6(12):3289-304. doi: 10.1111/j.1743-6109.2009.01464.x. Epub 2009 Sep 1.
With the advent of genetically modified mice, it seems particularly advantageous to develop a mouse model of diabetic erectile dysfunction.
To establish a mouse model of type I diabetes by implementation of either multiple low-dose streptozotocin (STZ) protocol or single high-dose STZ protocol and to evaluate morphologic alterations in the cavernous tissue and subsequent derangements in penile hemodynamics in vivo.
Eight-week-old C57BL/6J mice were divided into three groups: a control group, a group administered the multiple low-dose STZ protocol (50 mg/kg x 5 days), and a group administered the single high-dose STZ protocol (200 mg/kg).
After 8 weeks, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with hydroethidine (in situ analysis of superoxide anion), TUNEL, or antibodies to nitrotyrosine (marker of peroxynitrite formation), PECAM-1, smooth muscle alpha-actin, and phospho-eNOS. Penis specimens from a separate group of animals were used for phospho-eNOS and eNOS western blot or cGMP determination.
Erectile function was significantly less in diabetic groups than in control group. The generation of superoxide anion and nitrotyrosine and the number of apoptotic cells in both cavernous endothelial and smooth muscle cells were significantly higher in diabetic groups than in control group. Cavernous tissue phospho-eNOS and cGMP expression and the number of endothelial and smooth muscle cells were lower in diabetic groups than in control group. Both diabetic models resulted in similar structural and functional derangements in the corpus cavernosum; however, the mortality rate was higher in mice receiving single high-dose of STZ than in those receiving multiple low-doses.
The mouse model of type I diabetes is useful and technically feasible for the study of the pathophysiologic mechanisms involved in diabetic erectile dysfunction.
随着基因修饰小鼠的出现，开发糖尿病性勃起功能障碍的小鼠模型似乎具有特别的优势。
通过实施多次低剂量链脲佐菌素（STZ）方案或单次高剂量 STZ 方案，建立 I 型糖尿病小鼠模型，并评估海绵体组织的形态改变以及随后体内阴茎血液动力学的紊乱。
将 8 周龄 C57BL/6J 小鼠分为三组：对照组、多次低剂量 STZ 方案组（50mg/kg x 5 天）和单次高剂量 STZ 方案组（200mg/kg）。
8 周后，通过电刺激海绵体神经测量勃起功能。然后采集阴茎并进行羟乙基二氢吲哚（超氧阴离子原位分析）、TUNEL 或硝基酪氨酸（过氧亚硝酸盐形成的标志物）、PECAM-1、平滑肌α-肌动蛋白和磷酸化 eNOS 抗体染色。另一组动物的阴茎标本用于磷酸化 eNOS 和 eNOS 免疫印迹或 cGMP 测定。
与对照组相比，糖尿病组的勃起功能明显降低。与对照组相比，糖尿病组海绵体内皮和平滑肌细胞中超氧阴离子和硝基酪氨酸的产生以及凋亡细胞的数量明显增加。糖尿病组海绵体组织磷酸化 eNOS 和 cGMP 表达以及内皮和平滑肌细胞数量均低于对照组。两种糖尿病模型均导致海绵体结构和功能相似的紊乱；然而，单次高剂量 STZ 组的死亡率高于多次低剂量组。
I 型糖尿病小鼠模型对于研究糖尿病性勃起功能障碍涉及的病理生理机制是有用且技术上可行的。
