五味子醇甲治疗勃起功能障碍的机制研究

Schisandra chinensis Baill, a member of the Magnoliaceae family, has a long history of medical use as a tonic, a sedative, an antitussive and an antiaging drug in Asian countries. Our preliminary study showed 95% ethanol extract of Schisandra chinensis (Sch Ex.) and its Lignan constituent, schisandrol A (Sch A), relaxed penile corpus cavernosum in a dose-dependent manner in vitro penile perfusion model. The expressions of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) were significantly increased after incubation with Sch Ex. or Sch A. Moreover, Sch Ex. and Sch A also inhibited RhoA activity and Smad2 phosphorylation. These results suggest Sch A is a good candidate for treating erectile dysfunction (ED). This project will evaluate the effect of Sch A on ED and elucidate the underlying mechanism, clarify the interactions among NO/RhoA/TGFβ1 signaling pathways in a penile perfusion model in vitro and diabetes-induced ED rats in vivo. Our study will provide a reliable theoretical basis and lay a solid foundation for clinical application of Sch A.

申请者前期研究发现，五味子95%酒精提取物及其木酚素成分五味子醇甲在阴茎组织灌流实验中能够导致家兔阴茎海绵体平滑肌浓度依赖性舒张，上调海绵体内皮型一氧化氮合成酶（eNOS）和神经元型一氧化氮合成酶（nNOS）表达和提高组织内环磷酸鸟苷（cGMP）浓度，并且能够有效抑制RhoA活性和Smad2磷酸化。这些结果提示五味子醇甲可能对勃起功能障碍有良好的治疗作用，并且NO-cGMP，RhoA-Rho-kinase，TGFβ1-Smad2/3通路间可能存在交叉影响。本项目拟在前期研究基础上，通过活体组织体外实验和糖尿病勃起功能障碍大鼠体内实验两个层面，进一步观察五味子醇甲对于勃起功能障碍的治疗效果，阐明其作用机制，并揭示NO/RhoA/TGFβ1通路间的相互作用关系，为五味子醇甲的临床应用提供理论依据和科学基础。

申请者前期研究发现，五味子95%酒精提取物及其木酚素成分五味子醇甲在阴茎组织灌流实验中能够导致家兔阴茎海绵体平滑肌浓度依赖性舒张，上调海绵体内皮型一氧化氮合成酶（eNOS）和神经元型一氧化氮合成酶（nNOS）表达和提高组织内环磷酸鸟苷（cGMP）浓度，并且能够有效抑制RhoA活性和Smad2磷酸化。这些结果提示五味子醇甲可能对勃起功能障碍有良好的治疗作用，并且NO-cGMP，RhoA-Rho-kinase，TGFβ1-Smad2/3通路间可能存在交叉影响。本项目拟在前期研究基础上，通过活体组织体外实验和糖尿病勃起功能障碍大鼠体内实验两个层面，进一步观察五味子醇甲对于勃起功能障碍的治疗效果，阐明其作用机制，并揭示NO/RhoA/TGFβ1通路间的相互作用关系，为五味子醇甲的临床应用提供理论依据和科学基础。