泌乳素瘤性ED大鼠阴茎组织nNOS表达及超微结构变化的初步研究

Expression of n NOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction

目的:采用已烯雌酚(DES)诱导建立大鼠垂体泌乳素瘤勃起功能障(P-ED)模型,并研究泌乳素瘤ED大鼠阴茎n NOS表达及超微结构的变化。方法:取雄性Wistar大鼠,分为生理盐水对照组10只、花生油对照组10只及模型组20只。模型组腹腔内注射DES建立泌乳素瘤模型,8周后进行阿扑吗啡(APO)试验测定阴茎勃起功能筛选出P-ED大鼠模型。取垂体行病理学检查,并测定垂体质量、血清泌乳素(PRL)及睾酮(T)浓度。免疫组化法测定阴茎组织n NOS表达的变化,透射电镜观察阴茎海绵体组织超微结构变化。结果:APO试验共筛选出P-ED大鼠模型15只。与生理盐水及花生油对照组相比,注射DES 8周时大鼠垂体质量显著升高[(46.7±15.5)mg vs(11.7±2.4)、(12.4±2.3)mg,P均<0.05)];血清PRL浓度显著升高[(1 744.9±304.5)ng/ml vs(11.5±2.4)、(10.6±1.9)ng/ml,P均<0.01)];FT浓度降低[(1.54±0.46)ng/ml vs(3.11±1.08)、3.04±1.11)ng/ml,P均<0.05)]。与生理盐水及花生油对照组相比,注射DES 8周时大鼠阴茎勃起次数显著减少(16.7%vs 100%、vs 87.5%,P<0.05)。透射电镜下,8周时阴茎海绵体内皮细胞、平滑肌细胞等均有显著改变。与生理盐水及花生油对照组相比,P-ED组8周时阴茎组织n NOS表达平均光密度值(MOD)显著减少(0.024±0.011 vs 0.066±0.019、0.058±0.021,P均<0.05)。结论:阴茎组织超微结构的变化及n NOS表达减少可能是泌乳素瘤大鼠发生ED的主要机制。

Objective：To study the expression of n NOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction（ED）.Methods：We established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol（DES）and treated the control rats with normal saline（n = 10）or sterilized arachis oil（n = 10）.After 8weeks,we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin（PRL）and testosterone（T）to confirm the successful construction of the prolactinoma-induced ED model.Then we determined the expression of n NOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope.Results：The prolactinoma-induced ED model was successfully established in 15 rats.The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls（[46.7 ± 15.5] vs [11.7 ± 2.4] and [12.4 ± 2.3] mg,both P 〈0.05）.The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups（[1 744.9 ± 304.5]vs [11.5 ± 2.4]and [10.6 ± 1.9]ng / ml,both P 〈0.01; [1.54 ± 0.46]vs [3.11 ± 1.08]and [3.04 ± 1.11]ng / ml,both P 〈0.05）.The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls（16.7% vs100% and 87.5%,both P 〈0.05）,and so was the expression of n NOS in the penile tissue（0.024 ± 0.011 vs 0.066 ± 0.019 and0.058 ± 0.021,both P 〈0.05）.Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models.Conclusion：The ultrastructural changes of the penile cavernous tissue and the reduced expression of n NOS in penile tissue may be the most important mechanisms of prolactinomainduced ED in rats.