雄激素缺乏对大鼠阴茎海绵体H2S信号通路的影响  

Endogenous hydrogen sulfide and androgen deficiency-induced erectile dysfunction in rats

作　　者：左川[1] 黄一鸣[1] 姜睿[2] 杨海帆[2] 程波[2] 陈枫[1] 

机构地区：[1]泸州医学院附属医院,医学实验中心,四川泸州646000 [2]泸州医学院附属医院泌尿外科,四川泸州646000

出　　处：《中华男科学杂志》2014年第7期605-612,共8页National Journal of Andrology

基　　金：国家自然科学基金(81070486/H0415);2010年四川省杰出青年学术技术带头人培育计划(川科技[2010]4号:2010JQ0040)~~

摘　　要：目的:研究H2S信号通路在雄激素缺乏引起勃起功能下降中的作用。方法:8周龄健康雄性SD大鼠30只,随机分成6组:假手术2周组(A组)、假手术4周组(B组)、去势2周组(C组)、去势4周组(D组)、去势后雄激素替代治疗2周组(E组)和去势后雄激素替代治疗4周组(F组)。E、F去势术后给予生理剂量丙酸睾酮3 mg/(kg·d)皮下注射。测定各组大鼠血清睾酮、阴茎海绵体内压(ICP)、平均颈动脉压(MAP),测定血浆和阴茎组织内H2S浓度,免疫组化和Western印迹检测胱硫醚-β-合成酶(CBS)、胱硫醚-γ-裂解酶(CSE)蛋白的表达。结果:血清睾酮水平结果显示C组[(0.63±0.15)nmol/L]较A组[(16.55±4.17)nmol/L]、E组[(18.99±4.62)nmol/L]显著降低(P<0.05);D组[(0.70±0.22)nmol/L]较B组[(15.44±5.18)nmol/L]、F组[(20.99±6.41)nmol/L]显著降低(P<0.05)。予以5、7 V电刺激盆神经后,ICP/MAP在C组较A、E组显著降低(P<0.05),D组较B、F组显著降低(P<0.05)。血浆及阴茎组织内H2S浓度含量C组较A、E组显著降低(P<0.05),D组较B、F组显著降低(P<0.05)。免疫组化和Western印迹检测阴茎海绵体组织内CBS、CSE蛋白表达量,C组较A、E组显著降低(P<0.05),D组较B、F组显著降低(P<0.05)。C组较D组CBS、CSE蛋白表达量显著降低(P<0.05)。结论:阴茎海绵体组织CBS、CSE表达下降引起H2S信号通路受抑可能是雄激素缺乏引起大鼠勃起功能下降的机制之一。Objective： To investigate the role of endogenous hydrogen sulfide （H2 S） in erectile dysfunction （ED） induced by androgen deficiency. Methods ： We randomly divided 30 eight-week-old healthy male SD rats into six groups ： 2-week control （ A）, 4-week control （B）, 2-week castration （C）, 4-week castration （D）, 2-week castration ＋ androgen replacement （E）, and 4-week castration ＋ androgen replacement （F）, those in groups E and F subcutaneously injected with testosterone propionate （TP） at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone （T）, intracavernous pressure （ICP）, mean carotid arterial pressure （MAP） of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathi- onine-β-synthase （CBS） and cystathionine-γ-lyase （CSE） by imnlunohistochemistry and Western blot. Results： The serum T level was significantly lower in group C （ [0.63 ±0.15] nmol/L） than in A （ [16.55 ±4.17] nmol/L） and E （ [18.99 ±4.62] nmol/L） （P 〈0.05）, as well as in group D （ [0.70 ±0.22] nmol/L） than in B （ [15.44 ±5.18] nmol/L） and F （[20.99 ±6.41] nmol/L） （P 〈 0.05 ）, and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia （ P 〈 0.05 ）, H2 S concentration （ P 〈0. 05 ）, and the expressions of CBS and CSE （ P 〈 0.05 ）. The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D （P 〈 0. 05）. Conclusion ： The reduced expressions of CBS and CSE may inhibit the H2 S signalingpathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

关 键 词：硫化氢 信号通路 雄激素 勃起功能障碍 胱硫醚-Β-合成酶 胱硫醚-Γ-裂解酶 大鼠 

分 类 号：R698[医药卫生—泌尿科学]