HHcy ED大鼠血浆内Hcy的含量对阴茎海绵体CO/HO-2影响的研究

目的:研究高同型半胱氨酸血症(HHcy)勃起功能障碍大鼠体内一氧化碳/血红素加氧酶2(CO/HO-2)体系的变化。方法:雄性4周龄Wistar大鼠40只,体重280～310 g,正常喂养1周后,随机分为正常对照组(A组,10只),余30只给予3%蛋氨酸饲料4周后,测定尾静脉血Hcy,将Hcy>16.0μmol/L的大鼠确定为HHcy,由此确定造模成功。将模型组随机均分为B组(HHcy大鼠模型组,继续给予3%蛋氨酸饲料喂养),C组(HHcy盐酸甜菜碱治疗组,每天继续给予3%蛋氨酸饲料喂养,下午定时给予60 mg/kg甜菜碱,0.3 ml生理盐水溶液灌胃)和D组[每日给与锌卟啉IX腹腔内注射45μmol/(kg.d)],4周后处死大鼠提取标本血检测Hcy含量、阴茎海绵体中Hcy的含量及阴茎组织CO测定。分别于4周和8周2个时间点进行阿朴吗啡实验。结果:比较4组大鼠血浆Hcy浓度、阴茎勃起次数、阴茎海绵体组织CO浓度及阴茎组织血管中HO-2阳性细胞数量的检测结果,与A组[(12.55±0.82)μmol/L、(1.88±0.05)次、(10.55±1.73)μmol/L、6 059±1 257]比较,B组[(25.01±0.94)μmol/L、(0.70±0.05)次、(9.51±1.52)μmol/L、2 595±514]血浆中Hcy水平显著上升(P<0.05),阴茎勃起次数、CO的含量与HO-2阳性细胞均下降(P<0.05或P<0.01),并且Hcy与阴茎勃起次数呈负相关性(P<0.01);C组[(14.37±0.47)μmol/L、(1.18±0.08)次、(10.36±1.56)μmol/L、6 295±1 156]与B组比较,阴茎海绵体内Hcy含量下降,而CO与HO-2含量明显升高,阴茎勃起次数明显升高,有统计学意义(P<0.05或P<0.01)。结论:阴茎海绵体中的CO含量及阴茎海绵体HO-2表达减低可能是导致HHcy大鼠勃起功能障碍的原因之一。甜菜碱降低血浆Hcy浓度,增加阴茎海绵体中CO含量,是治疗HHcy勃起功能障碍的机制之一。

Effects of plasma Hcy on the contents of CO and HO-2 in the corpus cavernosum of ED rats with hyperhomocysteinemia

Objective: To study the changes in the activities of carbon monoxide(CO) and heme oxygenase 2(HO-2) in ED rats with hyperhomocysteinemia(HHcy).Methods: This study included 40 male Wistar rats weighing 280-310 g,10 as normal controls(group A).HHcy models were made in the other 30 by giving 3% methionine for 4 weeks,and then divided into groups B,C and D.The rats in group B continued to be fed with 3% methionine,those in group C were treated with betaine hydrochloride,and those in group D were given zinc porphyrin Ⅸ at 45 μmol per kg per d.Penile erections of the rats were recorded,and 4 weeks later,all were killed for determination of the levels of homocysteine(Hcy) in the blood plasma and the activities of CO and HO-2 in the corpus cavernosum of the penis.Results: The level of plasma Hcy,penile erection frequency and the content of CO in the corpus cavernosum were(12.55±0.82) μmol/L,(1.88±0.05) times and(10.55±1.73) μmol/L in group A,the Hcy level significantly higher while the penile erection frequency and CO content remarkably lower than in group B([25.01±0.94] μmol/L,[0.70±0.05] times and [9.51±1.52] μmol/L,P < 0.05 or P<0.01),with a negative correlation between the level of Hcy and that of CO and HO-2(P < 0.01).Compared with group B,the three parameters were all significantly increased in C([14.37±0.47] μmol/L,[1.18±0.08] times and [10.36±1.56] μmol/L,all P < 0.05 or P<0.01).Conclusion: Decreased expressions of CO and HO-2 in the corpus cavernosum of the penis may result in ED in HHcy rats.Betaine can reduce the Hcy level in the blood plasma and CO content in the corpus cavernosum,which might be one of the mechanisms of its action on ED with HHcy.