罗格列酮对泌乳素瘤性勃起功能障碍大鼠阴茎神经型一氧化氮合酶表达的影响

Effects of peroxisome proliferator-activated receptors-γligand of nNOS expression on penile tissue of erectile dysfunction rat models with prolactinoma

目的建立泌乳素瘤性勃起功能障碍大鼠模型(P-ED),研究过氧化物酶体增殖因子活化受体(PPAR-γ)配体罗格列酮对泌乳素瘤性勃起功能障碍大鼠阴茎神经型一氧化氮合酶(nNOS)表达的影响。方法雄性Wistar大鼠腹腔内注射乙烯雌酚(DES)建立泌乳素瘤模型。8周后进行阿扑吗啡(APO)试验,筛选出阴茎勃起功能障碍(ED)模型后,分为对照组、泌乳素瘤ED模型组、罗格列酮治疗组,免疫组化方法测定大鼠阴茎组织nNOS表达水平的变化。结果与对照组相比,注射DES 8周时大鼠阴茎勃起次数显著减少。12周时阴茎组织nNOS表达减少。罗格列酮治疗4周后血清PRL水平明显降低,阴茎组织nNOS表达增加。结论阴茎组织nNOS表达减少可能是泌乳素瘤大鼠发生ED的主要机制。罗格列酮能降低泌乳素瘤ED大鼠的PRL水平,改善阴茎勃起功能,增加阴茎nNOS表达。

Objective To establish rat models of erectile dysfunction caused by diethylstilbestrol（DES）-induced prolactinoma（prolactinoma erectile dysfunction,P-ED）,and to study the effects of rosiglitazone on the neuropathic nitric oxide synthase（nNOS）expression in penile tissue.Methods Male Wistar rats were peritoneally injected with DES to establish models of prolactinoma.After 8 weeks,the rats were injected with apomorphine to screen ED rats with DES-induced prolactinoma.Then the rats were divided into prolactinoma ED rats,rosiglitazone treatment group and control group.The changes of nNOS expression in penis were detected with immunohistochemistry.Results In week 8,the erectile ability of rats treated with DES was significantly reduced.In week12,the nNOS expression in the penis of DES-treated group was significantly lower than that in control group.The serum PRL level of rosiglitazone treatment group was significantly lower than that of the control group.The nNOS expression in the penis of rosiglitazone-treated group was significantly higher than the control group.Conclusions The reduction of nNOS in penis may be one of the most important mechanisms of ED with DES-induced prolactinoma.Rosiglitazone has therapeutic effects against ED of DES-induced prolactinoma：it could reduce the PRL level and increase the expression of nNOS in penis and improve erectile function.