Atorvastatin Or Testosterone Combined With Phosphodiesterase Type 5 Inhibitor For The Treatment Of Erectile Dysfunction Of Diabetic Rats

Objective 1. To establish the rat model of diabetes mellitus(DM) and evaluate the changes of erectile function of DM rats through time, in other words, to study the time-relevance of diabetes mellitus erectile dysfunction(DMED) 2. Based on the time-dependence of DMED, to evaluate the therapeutic effect of atorvastatin combined with chronic phosphodiesterase type 5(PDE5) inhibitor. 3. Based on the time-dependence of DMED, to evaluate the therapeutic effect of testosterone combined with chronic PDE5 inhibitor.Methods 1. DM SD rat models were established by peritoneal injection with streptozotocin(STZ, 50 mg/kg). The erectile functions were directly evaluated using electrostimulation of the cavernous nerve 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks and 6 weeks, respectively after the establishments of DM model. The corpus cavernosum tissues were processed with Masson staining and levels of endothelial nitric oxide synthase(e NOS), which is an erectile function indicator, were determined. The even-aged normal SD rats were used as control groups. 2. DMED rats were randomly divided into 4 groups: DMED without treatment(DM group), DMED with treatment of atorvastatin(DM+A group), DMED with treatment of chronic sildenafil(DM + S group) and DMED with treatment of atorvastatin combined with chronic sildenafil(DM+A+S group). Healthy rats served as controls. After the therapeutic cycle, the erectile functions were directly evaluated using electrostimulation of the cavernous nerve. The corpus cavernosum tissues were processed with Masson staining and levels of e NOS, which is an erectile function indicator, were determined. 3. DMED rats were randomly divided into 4 groups: DMED without treatment(DM group), DMED with treatment of testosterone(DM+T group), DMED with treatment of chronic sildenafil(DM + S group) and DMED with treatment of testosterone combined with chronic sildenafil(DM + T+S group). Healthy rats served as controls. After the therapeutic cycle, the erectile functions were directly evaluated using electrostimulation of the cavernous nerve. The corpus cavernosum tissues were processed with Masson staining and levels of e NOS, which is an erectile function indicator, were determined.Results 1. One week, 2 weeks, and 3 weeks after the establishments of DM model, there were no differences between the DM group and even-aged normal groups regarding erectile dysfunction. Four weeks, 5 weeks, and 6 weeks after the establishments of DM model, there were significant differences between the DM group and even-aged normal groups regarding erectile dysfunction. The results of western blot and immunohistochemistry indicated that the e NOS level was decreasing through time in the corpora cavernous of DM rats. 2. After the therapeutic cycle for the DMED rats, compared with control group(group N), the erectile function of diabetic rats(group DM) was significantly decreased. Atorvastatin(group DM+A) and chronic sildenafil treatment(group DM+S) could increase the erectile function of DM rats, and combined treatment with atorvastatin and sildenafil(group DM+A+S) had the most significant effect.The expression of e NOS had the same tendency. 3. After the therapeutic cycle for the DMED rats, compared with control group(group N), the erectile function of diabetic rats(group DM) were significantly decreased. Testosterone(group DM+T) and chronic sildenafil treatment(group DM+S) could increase the erectile function of DM rats, and combined treatment with atorvastatin and sildenafil(group DM+T+S) had the most significant effect. The expression of e NOS had the same tendency.Conclusions 1. The DM model induced by intraperitoneal injection with STZ(50 mg/kg) is stable and reliable. The model could be used as an important tool for the research of DMED and 4 weeks after the establishment of DM model could be used as the time point for the intervention experiments of DMED. 2. Atorvastatin combined with chronic PDE5 inhibitor can significantly improve DMED, and combined treatment is better than monotherapy of atorvastatin or chronic PDE5 inhibitor. 3. Testosterone combined with chronic PDE5 inhibitor can significantly improve DMED, and combined treatment is better than monotherapy of testosterone or chronic PDE5 inhibitor.