糖尿病大鼠阴茎海绵体组织中一氧化氮合酶亚型表达的研究

Expressions of NOS Isoforms in the Cavernous Tissues of Diabetic Rat Models

目的:通过观察糖尿病性雄性大鼠阴茎海绵体组织中一氧化氮合酶亚型(nNOS、iNOS、eNOS)表达和勃起功能的变化,以及应用胰岛素、α-硫辛酸(LA)干预对其的影响,进一步探讨糖尿病性ED发病机制,并为临床治疗提供新的思路。方法:将50只成年雄性SD大鼠分为4组:A组为正常对照组(10只),B组为糖尿病无干预组(13只),C组为糖尿病胰岛素干预组(12只),D组为糖尿病胰岛素+LA干预组(15只),采用腹腔注射链脲佐菌素法制作糖尿病模型。8周后各组大鼠通过注射阿朴吗啡后评价勃起功能并取阴茎海绵体组织用免疫组化EnV i-sion法观察海绵体组织中nNOS、iNOS、eNOS表达的变化。结果:A组大鼠勃起功能正常,勃起率100%;与A组相比,B组、C组、D组勃起功能水平显著降低(P<0.05),勃起率:B组28.6%,C组62.5%,D组80.9%,其海绵体组织中nNOS、eNOS表达显著降低,A组大鼠海绵体组织每视野nNOS、eNOS阳性神经纤维数为86.7、9.6,B组为36.5、3.3,C组为52.7、5.7,D组为71.4、7.4,而iNOS表达显著增加(P<0.05),A组为6.9,B组为43.6,C组为36.2,D组为19.3;与B、C组相比,D组勃起功能显著上升,海绵体组织中nNOS、eNOS表达均显著上升,iNOS显著下降(P<0.05)。结论:糖尿病严重影响阴茎勃起功能和nNOS、iNOS、eNOS的表达,高血糖是其发病基础之一,而LA对其有显著疗效,推测可能与其抗氧化作用机制有关。

Objective： To investigate the mechanism of diabetic erectile dysfunction（ED） and find new methods for its treatment by detecting the changes in nitric oxide synthase（NOS） isoforms and erectile function of diabetic rats and observing the effects of insulin and α-lipoic acid（LA） on it.Methods： Fifty male Sprague-Dawley rats were divided into Groups A（normal control,n = 10）,B（non-intervention diabetes mellitus,n = 13）,C（insulin intervention diabetes mellitus,n = 12）,and D（insulin ＋ LA intervention,n = 15）.And the diabetic models were made by intraperitoneal injection of streptozocin（STZ）.Eight weeks later,the erectile function of the rats was assessed following apomorphine injection and the contents of NOS isoforms in the erectile tissues measured by immunohistochemical staining.Results： All the rats of Group A showed a normal erectile function（100%）.In comparison,those in Groups B,C and D exhibited a significantly decreased rate,28.6% in Group B,62.5% in Group C and 80.9% in Group D.The numbers of positive nNOS fibers and eNOS in the penile tissues per visual field were 86.7 and 9.6 in Group A,but only 36.5 and 3.3 in Group B,52.7 and 5.7 in Group C,and 71.4 and 7.4 in Group D（P 0.05）.However,the expression of iNOS was significantly lower in Group A（6.9） than in Groups B（43.6）,C（36.2） and D（19.3）（P 0.05）.Compared with Groups B and C,the erectile function and the expressions of nNOS and eNOS were markedly increased,while the expression of iNOS significantly decreased in Group D（P 0.05）.Conclusion： Diabetes mellitus severely affects penile erectile function and the expressions of NOS isoforms in the cavernous tissues,for which hyperglycemia is mainly responsible.LA is proved obviously efficacious for diabetic ED,which might be related to its antioxidant effect.