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目的建立糖尿病性勃起功能障碍(DMED)大鼠模型,评价雄激素联合5型磷酸二酯酶抑制剂对DMED的治疗作用。方法通过链脲佐菌素(STZ)腹腔注射的方法建立DMED大鼠模型,造模成功4周后随机分为4组:DM组、DM补充睾酮组、DM补充西地那非组、DM补充睾酮联合西地那非组,正常大鼠作为对照组。给药6周后通过电刺激海绵体神经诱发勃起的方法测定各组大鼠的勃起功能,ELISA法测定各组大鼠的血清睾酮水平,HE染色和masson染色评价各组阴茎海绵体形态学改变,Western blot和免疫组织化学检测内皮型一氧化氮合酶(eNOS)的表达。结果 DM大鼠较正常大鼠勃起功能显著下降,睾酮水平明显降低,eNOS表达降低,阴茎海绵体间质纤维化程度增加而平滑肌成分减少。睾酮补充治疗和长期西地那非治疗均可改善DMED大鼠的勃起功能和改善DMED大鼠阴茎的纤维化程度,睾酮和长期西地那非联合治疗改善效果最明显。结论 DM大鼠的勃起功能明显降低,DMED发生的部分原因可能与雄激素水平降低有关,雄激素联合长期5型磷酸二酯酶抑制剂可明显改善DMED大鼠的勃起功能和阴茎纤维化程度。
Objective To establish a rat model of diabetic erectile dysfunction (DMED) and evaluate the therapeutic effect of androgen combined with type 5 phosphodiesterase inhibitor on DMED. Methods DMED rats were established by intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into 4 groups: DM group, DM supplemented with testosterone group, DM supplemented with sildenafil group, DM supplemented Testosterone combined sildenafil group, normal rats as control group. Eighteen weeks after administration, erectile function was detected by electrical stimulation of cavernous nerve erection. Serum testosterone level was measured by ELISA. HE staining and masson staining were used to evaluate the morphological changes of penis Western blot and immunohistochemistry were used to detect the expression of endothelial nitric oxide synthase (eNOS). Results Compared with normal rats, DM rats had significantly lower erectile function, decreased testosterone, decreased eNOS expression, increased interstitial fibrosis and decreased smooth muscle components in DM rats. Testosterone replacement therapy and long-term sildenafil treatment can improve DMED rat erectile function and improve the DME rat penile fibrosis, testosterone and long-term sildenafil combination therapy to improve the most obvious effect. Conclusions The erectile function of DM rats is obviously decreased. Part of the reason of DMED may be related to the decrease of androgen levels. Androgen and long-term phosphodiesterase type 5 inhibitors can significantly improve the erectile function and penile fibrosis of DMED rats.