雄激素调控RhoA/Rho激酶改善去势大鼠勃起功能障碍的机制研究

Androgen Improves Erectile Dysfunction by Regulating RhoA/Rho-kinase in Castrated Rats

目的探究雄激素调控RhoA/Rho激酶改善去势大鼠勃起功能障碍的机制。方法 40只健康8周龄SD雄性大鼠随机分成4组:A组为对照组;B组为实验组,给予手术切除双侧睾丸;C、D组为干预组,大鼠手术去势后每天给予不同浓度的十一酸睾酮(安特尔)灌胃(C组:20mg/kg,D组:10mg/kg),其余组给予等量的生理盐水。治疗8周后,检测大鼠血清睾酮浓度,海绵体测压评价大鼠勃起功能,Western blot检测大鼠阴茎海绵体S1P2/RhoA/Rho激酶的含量。结果相较于A组[(17.08±1.53)nmol/L]、C组[(15.47±1.62)nmol/L]和D组[(8.73±2.12)nmol/L]大鼠的血清睾酮浓度,B组[(1.34±0.62)nmol/L]明显降低(均P<0.05);海绵体测压结果显示B组MaxICP/MAP明显小于A组、C组和D组(均P<0.05);Western blot检测S1P2、RhoA、ROCK1和ROCK2的蛋白在B组表达明显高于A组、C组和D组(均P<0.05)。结论应用安特尔进行雄激素替代治疗可以通过抑制S1P2/RhoA/Rho激酶的激活,从而抑制阴茎海绵体平滑肌收缩,改善去势大鼠勃起功能。

Objective To investigate the mechanism of androgen regulating RhoA/Rho-kinase to improve erectile dysfunc- tion in castrated rats. Methods Forty eight-week-old healthy male SD rats were randomly divided into 4 groups ： control group （group A） experiment group（group B,in which rats were castrated） ;intervention groups （groups C and D, in which rats were treated with different concentrations of testosterone undecanoate orally every day at 20 mg/kg and 10 mg/kg, respectively after being castrated）. Animals in groups A and B were given 0.95 NS instead. After 8 week treatment,the level of serum testosterone,intracavernous pressure（ICP）and mean arterial pressure（MAP）were determined, and the expression of S1P2/RhoA/Rhokinase detected in the penis by Western blot. Results The level of serum testosterone was significantly lower in group B[（1.34 ±0.62）nmol/L]than in group A[（17. 084-1.53）nmol/L] ,group C[（15. 47±1.62）nmol/L]and group D[（8. 73±2.12）nmol/ L] （P〈0.05 for all） MaxICP/MAP was also lower in group B than in group A, group C and group D（P〈0. 05 for all） the expression levels of S1P2/RhoA/Rho-kinase were higher in group B than in groups A, C and D（P〈0.05 for all）. Conclusion Androgen replacement therapy can improve the erectile dysfunction by inhibiting the activation of S1P2/RhoA/Rho-kinase and thereby inhibiting the contraction of corpus cavernosum smooth muscle.