1-磷酸鞘氨醇受体1-3(S1P1-3)在去势雄性大鼠阴茎海绵体组织中的表达  

Expressions of S1P1- 3 in the corpus cavernosum of castrated male rats

作　　者：陈学勤[1,2] 夏纪毅[1] 程波[1] 姜睿[1] 

机构地区：[1]泸州医学院附属医院泌尿外科,四川泸州646000 [2]重庆市合川区中医院泌尿外科,重庆401520

出　　处：《中华男科学杂志》2016年第5期393-400,共8页National Journal of Andrology

基　　金：四川省科技厅基金(14JC0803);四川省教育厅基金(15ZA0164)~~

摘　　要：目的:探讨1-磷酸鞘氨醇受体1-3(S1P1-3)在去势雄性大鼠阴茎海绵体内的表达,及其与NOS/NO/c GMP、Rho A/Rho激酶等信号通路的关系。方法:18只8周龄健康雄性SD大鼠,随机分为去势组、对照组及去势后睾酮替代组(替代组)各6只,去势组和替代组大鼠切除双侧睾丸、附睾,替代组大鼠去势术后给予生理剂量丙酸睾酮3 mg/(kg·d)皮下注射4周,对照组为假手术组,去势组及对照组大鼠术后给予等量植物油皮下注射4周,12周龄时,测定各组大鼠阴茎海绵体内压/平均动脉压(ICPmax/MAP)、采用免疫组化和Western印迹分析S1P1-3、e NOS、P-e NOS、ROCK1、ROCK2在阴茎海绵体内的表达变化。结果:去势组大鼠血清睾酮水平[(0.41±0.04)nmol/L]显著低于对照组[(16.01±1.02)nmol/L]及替代组[(15.84±1.32)nmol/L](P<0.01),而替代组与对照组睾酮水平无显著差异。去势组ICPmax/MAP比值在0 V、3 V和5 V电刺激盆神经节时(0.088±0.014、0.323±0.014、0.432±0.012)均显著低于对照组(0.155±0.011、0.711±0.010、0.819±0.024)及替代组(0.153±0.012、0.696±0.017、0.763±0.027)(P<0.01),而对照组与替代组无显著差异。去势组S1P1、e NOS、P-e NOS的蛋白表达量[以目的蛋白占内参GAPDH的百分率表示:S1P1(49.99±3.39)%,e NOS(46.82±3.81)%,P-e NOS(45.42±4.35)%]显著低于对照组[S1P1(72.57±3.06)%,e NOS(89.76±3.98)%,P-e NOS(82.53±8.92)%]和替代组[S1P1(71.77±4.43)%,e NOS(87.19±4.23)%,P-e NOS(79.82±7.38)%](P<0.01),去势组S1P2、S1P3、ROCK1、ROCK2蛋白表达量[以目的蛋白占内参GAPDH的百分率表示:S1P2(82.35±4.13)%,S1P3(61.03±5.14)%,ROCK1(74.50±4.02)%,ROCK2(69.83±5.75)%]显著高于对照组[S1P2(41.67±1.68)%,S1P3(31.66±2.67)%,ROCK1(35.69±5.56)%),ROCK2(39.85±7.17)%]和替代组[S1P2(42.80±3.87)%,S1P3(32.25±4.22)%,ROCK1(38.06±5.21)%,ROCK2(42.36±4.44)%](P<0.01)。结论:雄激素缺乏导致大鼠ICPmax/MAP显著降低,可能与阴茎海绵体内S1P1表达下调、抑制e NOS/NO/c GMP信号通路,S1PObjective： To investigate the expressions of sphingosine-1-phosphate receptors 1- 3（ S1P1- 3） in the corpus cavernosum of castrated male rats and its relationship with the NOS / NO / c GMP and Rho A / Rho kinase signaling pathways. Methods：We equally randomized 18 eight-week-old healthy male SD rats into a sham-operation control,a castration,and a testosterone replacement（ TR） group and harvested the bilateral testes and epididymides from the rats in the latter two groups,followed by 4 weeks of subcutaneous injection of testosterone propionate at 3 mg per kilogram of the body weight per day for those in the TR group and that of plant oil for those in the control and castration groups. At the age of 12 weeks,we measured the serum testosterone（ T） level and maximum intracavernous pressure / mean arterial pressure（ ICPmax / MAP） of the animals and determined the expressions of S1P1- 3,e NOS,Pe NOS,ROCK1,and ROCK2 in the corpus cavernosum by Western blot and immunohistochemistry. Results： The serum T level was significantly decreased in the rats of the castration group as compared with those of the control and TR groups（ [0. 41 ± 0. 04] vs[16. 01 ± 1. 02]and [15. 84 ± 1. 32]nmol/L,P〈0. 01）,with no statistically significant difference between the latter two groups.The ICPmax / MAP at 0 V,3 V,and 5 V electric stimulation was remarkably lower in the rats of the castration group（ 0. 088 ± 0. 014,0. 323 ± 0. 014,and 0. 432 ± 0. 012） than in those of the control group（ 0. 155 ± 0. 011,0. 711 ± 0. 010,and 0. 819 ± 0. 024） and TR group（ 0. 153 ± 0. 012,0. 696 ± 0. 017,and 0. 763 ± 0. 027）（ P〈0. 01）,with no significant difference between the latter two groups. With GAPDH as internal control,the animals of the castration group showed markedly reduced expressions of S1P1（ [49. 99± 3. 39]%）,e NOS（ [46. 82 ± 3. 81]%）,and P-e NOS（ [45. 42 ± 4. 35]%） in comparison with those in the control group（ [72.57 ± 3. 06],[89. 76 ± 3. 98 ],and [82. 53 ± 8. 92]%）

关 键 词：1-磷酸鞘氨醇 1-磷酸鞘氨醇受体1-3 RHO激酶 内皮型一氧化氮合酶 去势 勃起功能障碍 大鼠 

分 类 号：R698[医药卫生—泌尿科学]