National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
J Sex Med. 2010 Oct;7(10):3351-64. doi: 10.1111/j.1743-6109.2010.01942.x.
With the advent of genetically engineered mice, it seems important to develop a mouse model of cavernous nerve injury (CNI).
To establish a mouse model of CNI induced either by nerve crushing or by neurectomy and to evaluate time-dependent derangements in penile hemodynamics in vivo and subsequent histologic alterations in the cavernous tissue.
Twelve-week-old C57BL/6J mice were divided into 4 groups (N=36 per group): control, sham operation, bilateral cavernous nerve crush, and bilateral cavernous neurectomy group.
Three days and 1, 2, 4, 8, and 12 weeks after CNI, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and TUNEL was performed. Immunohistochemical analysis was performed assaying for caspase-3, transforming growth factor-β1 (TGF-β1), phospho-Smad2, PECAM-1, factor VIII, and smooth muscle α-actin. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in endothelial cells or smooth muscle cells were counted.
Erectile function was significantly less in the cavernous nerve crushing and neurectomy groups than in the control or sham group. This difference was observed at the earliest time point assayed (day 3) and persisted up to 4 weeks after nerve crushing and to 12 weeks after neurectomy. The apoptotic index peaked at 1 or 2 weeks after CNI and decreased thereafter. Cavernous TGF-β1 and phospho-Smad expression was also increased after CNI. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in cavernous endothelial cells and smooth muscle cells were significantly greater in the cavernous nerve crush and cavernous neurectomy groups than in the control or sham group. Conclusion. The mouse is a useful model for studying pathophysiologic mechanisms involved in erectile dysfunction after CNI. Early intervention to prevent apoptosis in smooth muscle cells and endothelial cells or to inhibit cavernous tissue fibrosis is required to restore erectile function.
随着基因工程小鼠的出现，开发一种海绵体神经损伤（CNI）的小鼠模型似乎很重要。
建立一种通过神经挤压或神经切除术诱导的 CNI 小鼠模型，并评估体内阴茎血液动力学的时间依赖性紊乱以及随后海绵体组织的组织学改变。
将 12 周龄的 C57BL/6J 小鼠分为 4 组（每组 36 只）：对照组、假手术组、双侧海绵体神经挤压组和双侧海绵体神经切除术组。
CNI 后 3 天和 1、2、4、8 和 12 周，通过海绵体神经电刺激测量勃起功能。然后采集阴茎，进行 TUNEL 检测。进行免疫组织化学分析，检测半胱氨酸天冬氨酸蛋白酶-3（caspase-3）、转化生长因子-β1（TGF-β1）、磷酸化 Smad2、PECAM-1、因子 VIII 和平滑肌α-肌动蛋白。计数内皮细胞或平滑肌细胞中的凋亡细胞和磷酸化 Smad2 免疫阳性细胞的数量。
与对照组或假手术组相比，海绵体神经挤压和神经切除术组的勃起功能明显降低。这种差异在最早的检测时间点（第 3 天）就观察到了，并持续到神经挤压后 4 周和神经切除后 12 周。CNI 后凋亡指数在 1 或 2 周时达到峰值，随后下降。CNI 后海绵体 TGF-β1 和磷酸化 Smad 表达也增加。与对照组或假手术组相比，海绵体神经挤压和海绵体神经切除术组的海绵体内皮细胞和平滑肌细胞中的凋亡细胞和磷酸化 Smad2 免疫阳性细胞数量明显增加。结论：小鼠是研究 CNI 后勃起功能障碍相关病理生理机制的有用模型。需要早期干预以防止平滑肌细胞和内皮细胞凋亡或抑制海绵体组织纤维化，以恢复勃起功能。
