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RhoA/Rho激酶在大鼠阴茎勃起机制中的调节作用 被引量:11

The Effect of RhoA/Rho-kinase in the Regulation ofPenile Erection of Rats
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摘要  一般认为一氧化氮(nitricoxide,NO)释放增加促进小动脉和海绵体平滑肌舒张是导致男性阴茎勃起的主要机制.研究发现内源性血管收缩因子对维持阴茎萎软状态有重要作用.应用大鼠模型活体检测使用Y 27632拮抗Rho 激酶活性后对阴茎勃起生理机制的影响;应用免疫转印技术检测阴茎海绵体内RhoA和Rho激酶蛋白的表达.结果显示在大鼠海绵体组织内有内源性RhoA和Rho激酶蛋白的表达和存在;Y 27632海绵体内注射阻滞RhoA/Rho激酶活性使ICP和CCP/MAP比值明显升高;局部小剂量应用Y 27632对MAP没有明显影响;Y 27632可增强系列电刺激引起的由NO介导的CCP/MAP比值的增加;NO合成酶和鸟苷酸环化酶抑制剂的作用不能阻滞RhoA/Rho激酶抑制剂对大鼠阴茎海绵体平滑肌的松弛作用和CCP/MAP的增加.说明RhoA/Rho激酶信号系统发挥了维持海绵体萎软状态重要作用,这是与NO介导途径不同的阴茎勃起生理调节机制.RhoA/Rho激酶抑制剂可能是ED治疗的新领域新方法. As we knew, the release of nitric oxide (NO) caused by erectile stimulation could initiate cavernosal arterioles and sinuses' smooth muscle relaxation, resulting in penile erection. During recent years, NO_mediated pathway was always thought to be the principal machanism leading to male erection. Evidence also existed implicating the important role of many vasoconstrictors in the regulation of cavernosal tone and maintained the penis in flaccid. With the animal experiment, we investigated the effect of inhibiting of RhoA/Rho kinase on erectile response of rats. Meanwhile, the existence of RhoA/Rho kinase proteins was examined with Western_blot analysis. Using immunoblot analysis, we confirmed that endogenous RhoA/Rho kinase was present in rat cavernosal tissue. With the application of Y?27632, the ratio of CCP/MAP could be enhanced greatly after the RhoA/Rho kinase was blocked. In the mean_time, it had no significant influence on MAP with small dose of Y?27632 injected into cavernosal. Also Y?27632 might enhance the increas of CCP/MAP which was voltage_induced, NO_mediated. These enhancements couldn't be attenuated or inhibited with the presence of inhibitors of NO synthase and guanylate cyclase. Our results suggested that RhoA/Rho kinase pathway played an important role in maintaining the flaccid of penis on rats. The antagnism of the activativity of RhoA/Rho kinase pathway was independent of NO_mediated pathway to cause erectile response of penis. It introduces to us a potential alternate avenue for the treatment of erectile dysfunction.
出处 《南京大学学报(自然科学版)》 CAS CSCD 北大核心 2002年第5期620-626,共7页 Journal of Nanjing University(Natural Science)
基金 江苏省社会发展项目(BS2001066) 江苏省"135"工程人才基金 2000年国际性功能障碍研究学会(ISIR)青年研究基金
关键词 调节作用 大鼠 阴茎勃起 RHOA/RHO激酶 血管收缩因子 生理机制 免疫转印技术 penile erection, RhoA/Rho kinase,vasoconstrictor
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