ED 29. The role of TGF - β1/Smad/CTGF pathway in the fibrous - muscular alterations of corpus cavernosum related to streptozotocin - induced diabetic

In this study, we investigated the pathological changes of extracellular matrix in the corpus cavernosum of streptozotocin (STZ)-induced diabetes rats, and examined the mechanisms underlying changes in mechanical properties of the penile erection due to diabetic erectile dysfunction (ED), the role of TGF-β1/Smad/CTGF pathway. Forty 8-week-old Sprague- Dawley rats were used and randomly divided into control and diabetic groups. Diabetes was induced by an intraperitoneal injection of STZ (60 mg/kg). Eight weeks later, the erectile function was measured by electrical stimulation of the cavernous nerve by MP150 system. The penis was harvested and histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain and immunohistochemical stain) and western blot were performed followed by Intracavernous pressure (ICP)/mean arterial pressure (MAP) assays. Diabetes significantly attenuated the erectile responses with decreased corpus cavernosum (CC) smooth muscle/collagen ratio. Cavernous collagen fibersⅠ/Ⅲ ratio was significantly higher in diabetic rats than in controls. Cavernous elastic fibers manifest as fragmentation in diabetic rats, the length was shorter. TGF-β1/Smad/CTGF signaling pathway was up-regulated in the penis from diabetic rats. Compared with that in control rats, P-Smad2 expression was higher mainly in smooth muscle cells and fibroblasts of diabetic rats; the apoptotic index was higher in diabetic rats, compared with the control group. The upregulation of TGF-β1/Smad/CTGF signaling pathway in the penis of diabetic rats might play an important role in diabetesinduced structural changes and deterioration of erectile function.