Anatomy Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Urology. 2013 Jun;81(6):1253-9. doi: 10.1016/j.urology.2012.12.068.
To assess the effect of chronic low-dose administration of tadalafil (Td) on penile cavernous tissue in induced diabetic rats.
The study investigaged 48 adult male albino rats, comprising a control group, sham controls, streptozotocin-induced diabetic rats, and induced diabetic rats that received Td low-dose daily (0.09 mg/200 g weight) for 2 months. The rats were euthanized 1 day after the last dose. Cavernous tissues were subjected to histologic, immunohistochemical, morphometric studies, and measurement of intracavernosal pressure and mean arterial pressure in anesthetized rats.
Diabetic rats demonstrated dilated cavernous spaces, smooth muscles with heterochromatic nuclei, degenerated mitochondria, vacuolated cytoplasm, and negative smooth muscle immunoreactivity. Nerve fibers demonstrated a thick myelin sheath and intra-axonal edema, where blood capillaries exhibited thick basement membrane. Diabetic rats on Td showed improved cavernous organization with significant morphometric increases in the area percentage of smooth muscles and elastic tissue and a significant decrease of fibrous tissue. The Td-treated group showed enhanced erectile function (intracavernosal pressure/mean arterial pressure) at 0.3, 0.5, 1, 3, and 5 Hz compared with diabetic group values at the respective frequencies (P <.05) that approached control values.
Chronic low-dose administration of Td in diabetic rats is associated with substantial improvement of the structure of penile cavernous tissue, with increased smooth muscles and elastic tissue, decreased fibrous tissue, and functional enhancement of the erectile function. This raises the idea that the change in penile architecture with Td treatment improves erectile function beyond its half-life and its direct pharmacologic action on phosphodiesterase type 5.
评估慢性低剂量他达拉非(Td)给药对诱导型糖尿病大鼠阴茎海绵体组织的影响。
本研究共纳入 48 只成年雄性白化大鼠,包括对照组、假手术对照组、链脲佐菌素诱导的糖尿病大鼠组以及接受每日 0.09mg/200g 体重 Td 低剂量治疗 2 个月的诱导型糖尿病大鼠组。最后一次给药后 1 天处死大鼠。对海绵体组织进行组织学、免疫组织化学、形态计量学研究,并测量麻醉大鼠的海绵体内压和平均动脉压。
糖尿病大鼠的海绵体空间扩张,平滑肌出现异染色质核、退变的线粒体、空泡化的细胞质和平滑肌免疫反应阴性。神经纤维表现出厚的髓鞘和轴内水肿,而毛细血管显示出厚的基底膜。接受 Td 治疗的糖尿病大鼠的海绵体组织结构得到改善,平滑肌和弹性组织的面积百分比显著增加,纤维组织显著减少。与相应频率下糖尿病组相比,Td 治疗组在 0.3、0.5、1、3 和 5Hz 时的勃起功能(海绵体内压/平均动脉压)显著增强(P<0.05),接近对照组值。
在糖尿病大鼠中给予慢性低剂量 Td 可显著改善阴茎海绵体组织的结构,增加平滑肌和弹性组织,减少纤维组织,并增强勃起功能。这表明,与 Td 治疗改善勃起功能的半衰期及其对磷酸二酯酶 5 的直接药理作用有关,其对阴茎结构的改变可改善勃起功能。