褪黑素对糖尿病性勃起功能障碍大鼠的神经保护作用及可能的机制研究  

Neuroprotective effects and the possible mechanism of melatonin on erectile dysfunctionin streptozotocin-induced diabetic rats

作　　者：惠宇[1] 周峰[1] 雷洪恩[2] 杨璧铖[2] 辛钟成[2] 侯建全[1] 

机构地区：[1]苏州大学附属第一医院泌尿外科,江苏苏州215006 [2]北京大学第一医院男科中心,北京100034

出　　处：《现代泌尿外科杂志》2016年第4期301-306,共6页Journal of Modern Urology

基　　金：国家自然科学基金(No.81300478);江苏省自然科学基金(No.BK20130269);江苏省卫生厅医学科研项目(No.H201312);苏州市科学发展计划项目(No.SYS201450)

摘　　要：目的探讨褪黑素(melatonin,MT)对糖尿病性勃起功能障碍大鼠的神经保护作用及可能机制。方法 28只SD大鼠腹腔注射链脲佐菌素建立糖尿病模型,8周后,糖尿病(diabetes mellitus,DM)大鼠随机分为DM组和MT组,分别每天腹腔注射磷酸盐缓冲液(PBS)和MT。另外12只正常大鼠为N组,每天腹腔注射PBS。治疗4周后,检测各组大鼠阴茎海绵体内压、平均动脉压、阴茎背神经(dorsal penile nerve,DPN)和盆神经节(major pelvic ganglion,MPG)病变情况。对阴茎海绵体纤维化情况、丙二醛含量、超氧化物歧化酶活性、p38和p-p38水平也进行了测定。结果 DM组糖尿病大鼠勃起功能明显下降,DPN和MPG发生了明显的神经退行性病变,同时阴茎海绵体内胶原蛋白沉积增多,氧化应激和p-p38蛋白水平升高。褪黑素治疗显著提高了糖尿病大鼠的勃起功能,改善DPN和MPG神经病变,减少胶原纤维沉积并且降低了氧化应激与p-p38蛋白水平。结论 MT治疗可以有效提高糖尿病大鼠的勃起功能,改善阴茎背神经、盆神经节病变,减轻阴茎纤维化情况。其机制可能是通过降低糖尿病大鼠阴茎内氧化应激水平以及抑制p38MAPK信号通路。Objective To explore the neuroprotective effects and possible mechanism of melatonin（MT）on erectile dysfunction in streptozotocin-induced diabetic rats.Methods A total of 28 SD rats received intraperitoneal injection of streptozotocin.After 8 weeks,the determined diabetic rats were randomly divided into2 groups：DM group（which received intraperitoneal injection of phosphate buffer solution（PBS）daily）,and MT group（which received MT injection）.Another 12 normal rats served as controls and received PBS treatment daily.After 4 weeks,intracavernous pressure（ICP）,mean arterial pressure（MAP）,pathological changes in penis and major pelvic ganglion（MPG）were measured in all rats.Malondialdehyde（MDA）,superoxide dismutase（SOD）,p38 and p-p38 levels in penis were detected.Results Diabetic rats showed significant decreases of erectile function accompanied with serious neuropathy in dorsal penile nerve（DPN）and MPG;meanwhile,collagen deposition,oxidative stress and p-p38 levels in penis were elevated.Melatonin treatment partially but significantly improved the erectile function,ameliorated neuropathy in DPN and MPG,decreased collagen deposition,oxidative stress and pp38 levels in diabetic rats.Conclusions Melatonin treatment can improve erectile function,ameliorate neuropathy and fibrosis in diabetic rats.The underlying mechanism may involve regulating oxidative stress and inhibiting p38 MAPK signaling pathway.

关 键 词：勃起功能障碍 糖尿病 褪黑素 神经保护作用 抗氧化 P-P38 

分 类 号：R587.2[医药卫生—内分泌]