糖尿病性勃起功能障碍多因素发病机制研究

The Study of Multifactorial Pathogenesis of Diabetic Erectile Dysfunction

从神经、血管、代谢、离子通道等多个角度出发,研究糖尿病性勃起功能障碍(DMED)的发病机制,为开展DMED的综合治疗临床研究提供前期研究基础.成年雄性SD大鼠50只,随机取35只大鼠用于制作糖尿病模型,其余大鼠作为正常对照.饲养8周后,用阿朴吗啡法筛选DMED大鼠,用电刺激勃起神经测定海绵体内压(ICP)方法评价勃起功能.取正常组和DMED组大鼠的阴茎海绵体组织,分成若干份,用免疫组化法测定海绵体组织一氧化氮合酶(NOS)的3种亚型(nNOS,eNOS,iNOS)的变化;用Western Blot法测定神经生长因子(NGF)在海绵体组织的表达差异;用放射免疫法测定海绵体组织血管紧张素II(AngII)含量差异;用Western Blot法测定血管内皮生长因子(VEGF)和缝隙连接蛋白Connexin-43含量差异.与正常对照组相比,DMED大鼠ICP测定值明显降低;海绵体组织中nNOS、eNOS表达明显降低,而iNOS表达明显增加;NGF蛋白表达明显增加;血管紧张素II水平显著升高;VEGF蛋白表达明显减少;Connexin-43蛋白表达减少.以上试验结果说明DMED发病机制复杂,与神经、血管、代谢、离子通道等均有关.提示在今后临床治疗研究和实践中,应该从各个角度出发,针对多因素发病机制,采用综合治疗的方法,以提高疗效.

In order to direct treatment research on diabetic erectile dysfunction （ED）, we studied the pathogenesis of diabetic erectile dysfunction from several factors such as neural factor, vascular factor and ion tunnel. Male Sprague-Dawley rats were injected with 65 mg/kg streptozotocin to induce diabetes mellitus （DM）. Eight weeks later, the erection function of the rats were measured by apomorphine injection. The intercavernous pressure （ICP） of the normal and diabetic rats with ED were measured by electrostimulation before being sacrificed. Each peeled penis was divided into several parts. We detected the three subtypes of nitric oxide synthase （NOS） in cavernous tissues of normal and diabetic ED rats, including neural NOS （nNOS）, endothelial NOS （eNOS）, induced NOS （iNOS）, by immunohistochemistry. The level of angiotension Ⅱ （AngⅡ） was dectected by radioimmunoassay. Then we used Western Blot analysis to detect the distribution of nerve growth factor （NGF）, vascular endothelial growth factor （VEGF） and connexin-43 in cavernous tissues. Comparing the result with that of normal rates, we found that the mean of ICP in diabetic ED rats was significantly decreased. The positive staining cells of eNOS and nNOS were significantly decreased while that of iNOS was increased. The protein expression of NGF was up-regulated. The AnglI level in cavernous was significantly raised. The protein expression of VEGF and connexin 43 was downregulated. In conclusion, we found that the pathogenesis of diabetic ED was very complex, involved in nerve, neurotransmitter, blood vessel, endothelial function, metabolism, endocrine and so on. In our basic researches and clinical work, we should use combined therapy according to the multifactorial pathogenesis of diabetic ED, in order to elevate the therapeutic effect.