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低雄激素状态通过抑制大鼠阴茎海绵体中Tie2的表达来损害勃起功能。

[A low androgen state impairs erectile function by suppressing the expression of Tie2 in rat penile cavernosa].

作者信息

Liu Jia, Jiang Rui

机构信息

Department of Urology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000 Sichuan, China.

Public Experimental Technology Center, Southwest Medical University, Luzhou, 646000 Sichuan, China.

出版信息

Zhonghua Nan Ke Xue. 2023 Aug;29(8):675-681.

Abstract

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 1×108TU/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.

摘要

目的

探讨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)调节大鼠阴茎海绵体组织中内皮型一氧化氮合酶(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、去势+睾酮替代组(去势+T组,去势后每隔一天皮下注射丙酸睾酮3mg/kg)、假手术+Tie2转染组(假手术+Tie2组,去势4周后向大鼠阴茎海绵体内注射20μl Tie2基因慢病毒,滴度为1×108TU/ml)、去势+Tie2组、去势+空载体组。去势5周后,测量各组大鼠阴茎海绵体内最大压力与平均动脉压之比(ICPmax/MAP)、血清睾酮(T)、一氧化氮(NO)以及阴茎海绵体中Tie2、AKT、磷酸化AKT(P-AKT)、eNOS和磷酸化eNOS(P-eNOS)的表达水平。

结果

去势组阴茎海绵体组织中T、NO含量及ICPmax/MAP均显著低于假手术组(P<0.01)。转染过表达Tie2的慢病毒后,去势+Tie2组的NO含量及ICPmax/MAP显著高于去势组(P<0.01)。去势组大鼠阴茎海绵体组织中Tie2、P-AKT/AKT及P-eNOS/eNOS的表达显著低于假手术组,而去势+Tie2组中Tie2、P-AKT/AKT及P-eNOS/eNOS的表达显著高于去势组。

结论

雄激素缺乏可能通过抑制Tie2/AKT/eNOS信号通路,降低阴茎海绵体组织中P-eNOS/eNOS和NO的浓度,从而抑制阴茎勃起。上调阴茎海绵体组织中Tie2的表达可增加P-AKT/AKT、P-eNOS/eNOS和NO的浓度,改善勃起功能障碍。

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