2型糖尿病大鼠血浆同型半胱氨酸与阴茎海绵体内NOS和内源性CO的相关性研究

Correlation of homocysteine in plasma with NOS and endogenous CO in the penile corpus cavernosum of type 2 diabetic rats

目的:研究2型糖尿病性大鼠血浆同型半胱氨酸(Hcy)与阴茎海绵体内NOS和内源性CO的相关性。方法:选取3月龄雄性Wistar大鼠50只,随机选取10只为对照组(A组);高糖高脂饲料饲养4周后从其他40只大鼠中筛选出30只构建成功的糖尿病(DM)大鼠模型,随机分成3组:DM大鼠组(B组);胰岛素治疗组(C组)和叶酸+维生素B12治疗组(D组)。8周及12周后注射阿朴吗啡观察各组大鼠阴茎勃起情况。12周后测各组大鼠血浆总Hcy含量及阴茎海绵体内NOS活性和CO含量。结果:与A组比较,B组大鼠血浆Hcy浓度明显升高,阴茎勃起功能明显降低,阴茎海绵体NOS活性和CO含量均下降,差异有显著性(P<0.01)。2型DM大鼠中高Hcy血症发生率为55%。与B组比较,C组和D组中大鼠血浆Hcy浓度显著下降,阴茎勃起功能、阴茎海绵体NOS活性均升高(P<0.01),Hcy与NOS(rA=-0.89,rB=-0.76,rC=-0.91,rD=-0.91)及CO含量(rA=-0.82,rB=-0.77,rC=-0.93,rD=-0.81)均呈负相关。结论:2型DM大鼠血浆中的高Hcy可能是引起阴茎海绵体NOS活性下降、CO含量下降,进而导致DM ED发病的分子机制之一。胰岛素、叶酸和维生素B12可以改善DM大鼠的勃起功能,提高阴茎海绵体NOS活性和CO含量。

Objective： To study the correlation of homocysteine（Hcy） in plasma with nitric oxide synthetase（NOS） and endogenous carbon monoxide（CO） in the penile corpus cavernosum of type 2 diabetic rats.Methods： This study included 40 male Wistar rats,10 as controls（Group A） and the other 30 as diabetes mellitus（DM） models.Four weeks after the model establishment,the model rats were divided into a DM group（Group B,n=10）,an insulin treated group（Group C,n=10）,and a folic acid and vitamin B12 treated group（Group D,n= 10）.All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks,and the levels of total plasma Hcy（tHcy）,NOS and CO in the penile corpus cavernosum were measured at 12 weeks.Results： Compared with Group A,the level of tHcy was significantly increased,while NOS and CO activities in the penile cavernous tissue and erectile function remarkably decreased in Group B（P0.01）.The incidence rate of high Hcy was 55% in the DM rats.In comparison,the level of tHcy was obviously decreased,and the NOS activity and erectile function markedly increased in Groups C and D（P0.01）.The Hcy level showed a significant negative correlation with NOS activity（r_A=-0.89,r_B =-0.76,r_C =-0.91,r_D =-0.91） and CO content（r_A=-0.82,r_B=-0.77,r_C =-0.93,r_D =-0.81）.Conclusion： High plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum,and consequently induce erectile dysfunction in DM rats,while insulin,folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.