低雄激素通过抑制大鼠阴茎海绵体组织Tie2的表达抑制勃起功能

A low androgen state impairs erectile function by suppressing Tie2 in rat penile cavernosa

目的:研究雄激素是否通过富含内皮的外膜内皮细胞激酶2(Tie2)/磷酸激酶(AKT)调控大鼠阴茎海绵体组织内皮一氧化氮合酶(eNOS)的表达,并影响阴茎勃起功能。方法:将8周龄雄性SD(Sprague Dawley)大鼠随机分为6组(n=6):假手术组、去势组、睾酮替代组(去势1 d后隔日1次丙酸睾酮3 mg/kg皮下注射)、假手术+Tie2转染组(去势术后4周大鼠阴茎海绵体注射20 ul携带Tie2基因的慢病毒,滴度1×10^(8)TU/ml)、去势+Tie2转染组、去势+空载体组。去势术后5周,测定各组大鼠的最大阴茎海绵体内压与平均动脉压比值(ICPmax/MAP)、血清睾酮(T)水平、一氧化氮(NO)含量,以及Tie2、AKT、P-AKT、eNOS、P-eNOS在各组大鼠阴茎海绵体中的表达水平。结果:去势组大鼠的T、阴茎海绵体组织中NO的含量和ICPmax/MAP明显低于假手术组大鼠(P<0.01)。而经过Tie2过表达慢病毒转染后,去势+Tie2组大鼠的NO含量及ICPmax/MAP明显高于去势组大鼠(P<0.01)。去势组大鼠阴茎海绵体组织中Tie2的表达及P-AKT/AKT和P-eNOS/eNOS明显低于假手术组大鼠,去势+Tie2组大鼠的Tie2的表达及P-AKT/AKT和P-eNOS/eNOS明显高于去势组大鼠。结论:低雄激素可能通过抑制Tie2/AKT/eNOS信号通路,降低阴茎海绵体组织P-eNOS/eNOS和NO浓度,抑制阴茎勃起。上调阴茎组织海绵体组织中Tie2的表达可以提高P-AKT/AKT、P-eNOS/eNOS和NO浓度,改善ED。

Objective:To investigate whether androgens regulate the expression of endothelial nitric oxide synthase(eNOS)in rat penile cavernous tissue through endothelial-rich adventitial endothelial cell kinase 2(Tie2)/phosphokinase(AKT)and affect penile erectile function.Methods:Eight-week-old male SD(Sprague Dawley)rats were randomly divided into 6 groups(n=6):sham group,cast group,cast+testosterone replacement group(cast+T group,subcutaneous injection of testosterone propionate 3mg/kg every other day after castration),sham+Tie2 transfection group(sham+Tie2 group,20ul Tie2 gene lentivirus injection into penile cavernosa of rats 4 weeks after castration,titer 1×10^(8)TU/ml),cast+Tie2 group,cast+empty vector group.Five weeks after castration,the ratio of maximum penile intracavernous pressure to mean arterial pressure(ICPmax/MAP),serum testosterone(T),nitric oxide(NO),and the expression levels of Tie2,AKT,P-AKT,eNOS and P-eNOS in the corpus cavernosa of the penis in each group of rats were measured.Results:The contents of T、NO and ICPmax/MAP in the penile cavernous tissues of the cast group were significantly lower than the sham group(P<0.01).After transfection with Tie2 overexpressing lentivirus,the NO content and ICPmax/MAP of the cast+Tie2 group were significantly higher than the cast group(P<0.01).The expression of Tie2 and P-AKT/AKT and P-eNOS/eNOS in penile cavernous tissue of rats in the cast group were significantly lower than those in the sham group,and the expression of Tie2 and P-AKT/AKT and P-eNOS/eNOS in the cast+Tie2 group were significantly higher than the cast group.Conclusion:Hypoandrogen may inhibit penile erection by inhibiting the Tie2/AKT/eNOS signaling pathway,reducing the concentration of P-eNOS/eNOS and NO in penile cavernous tissue.Up-regulating the expression of Tie2 in penile cavernous tissue can increase the concentrations of P-AKT/AKT,P-eNOS/eNOS and NO,and improve ED.