摘要
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。
ABSTRACT：Objective To establish the rat model of diabetes mellitus erectile dysfunction （DMED） and evaluate the ther‐apeutic effect of androgen combined with phosphodiesterase type 5 （PDE5） inhibitor .Methods DMED models were estab‐lished by peritoneal injection of streptozotocin （STZ） .Four weeks later the DMED rats were randomly divided into 4 groups：DM group ,testosterone group ,sildenafil group ,and testosterone plus sildenafil group .Healthy rats served as controls .Six weeks after the initiation of treatments ,the erectile function of each group was evaluated using electrostimulation of the cav‐ernous nerve .The serum testosterone levels were determined with enzyme‐linked immunosorbent assay （ELISA） .The morpho‐logical changes of corpus cavernosum of penis were evaluated with hematoxylin‐eosin staining and masson staining .The endo‐thelial nitric oxide synthase （eNOS） level were determined with Western blot and immunohistochemistry .Results Compared with healthy rats ,the erectile function ,testosterone level and eNOS level of diabetic rats were significantly decreased .The smooth muscle cells of diabetic rats＇corpus cavernosum were reduced while extracellular matrix fibrosis was increased .Testos‐terone replacement and chronic sildenafil treatment could ameliorate erectile function and extracellular matrix fibrosis ,and combined treatment with testosterone and sildenafil had the most significant effect .Conclusions The erectile function of DM rats is significantly impaired .The pathogenesis of DMED may be partly attributed to the low androgen level .Combined treatment of testosterone and sildenafil can significantly improve erectile function and extracellular matrix fibrosis of DMED rats .
出处
《现代泌尿外科杂志》
CAS
2015年第5期347-352,共6页
Journal of Modern Urology
基金
国家自然科学基金面上项目(No.81270695
81472379)
关键词
糖尿病
勃起功能障碍
雄激素
磷酸二酯酶抑制剂
diabetes mellitus
erectile dysfunction
androgen
phosphodiesterase inhibitor
