Abstract：
BACKGROUND: Diabetes mellitus erectile dysfunction (DMED) is one of common complications of diabetes. We aimed to investigate the potential efficacy of methyl protodioscin (MPD) in DMED and explored the underlying mechanism.
METHODS: Diabetic mice were induced by streptozotocin, while vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were stimulated with high glucose. MPD was administrated in vitro and in vivo to verify its efficacy on DMED. The interaction of c-Myc and AKAP12 was determined by luciferase reporter assay and chromatin immunoprecipitation assay.
RESULTS: c-Myc and AKAP12 were upregulated in penile tissues in DMED mice. In high glucose-stimulated VSMCs or VECs, MPD intervention enhanced cell viability, inhibited apoptosis, decreased c-Myc and AKAP12, as well as elevated p-eNOS Ser1177. MPD-induced apoptosis inhibition, AKAP12 reduction and p-eNOSSer1177 elevation were reversed by AKAP12 overexpression. c-Myc functioned as a positive regulator of AKAP12. Overexpression of c-Myc reversed the effects induced by MPD in vitro, which was neutralized by AKAP12 silencing. MPD ameliorated erectile function in diabetic mice via inhibiting AKAP12.
CONCLUSIONS: MPD improved erectile dysfunction in streptozotocin-caused diabetic mice by regulating c-Myc/AKAP12 pathway, indicating that MPD could be developed as a promising natural agent for the treatment of DMED.
METHODS: Diabetic mice were induced by streptozotocin, while vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were stimulated with high glucose. MPD was administrated in vitro and in vivo to verify its efficacy on DMED. The interaction of c-Myc and AKAP12 was determined by luciferase reporter assay and chromatin immunoprecipitation assay.
RESULTS: c-Myc and AKAP12 were upregulated in penile tissues in DMED mice. In high glucose-stimulated VSMCs or VECs, MPD intervention enhanced cell viability, inhibited apoptosis, decreased c-Myc and AKAP12, as well as elevated p-eNOS Ser1177. MPD-induced apoptosis inhibition, AKAP12 reduction and p-eNOSSer1177 elevation were reversed by AKAP12 overexpression. c-Myc functioned as a positive regulator of AKAP12. Overexpression of c-Myc reversed the effects induced by MPD in vitro, which was neutralized by AKAP12 silencing. MPD ameliorated erectile function in diabetic mice via inhibiting AKAP12.
CONCLUSIONS: MPD improved erectile dysfunction in streptozotocin-caused diabetic mice by regulating c-Myc/AKAP12 pathway, indicating that MPD could be developed as a promising natural agent for the treatment of DMED.
摘要：
背景：糖尿病勃起功能障碍（DMED）是糖尿病的常见并发症之一。我们的目的是研究甲基原薯林（MPD）在DMED中的潜在功效，并探讨其潜在机制。
方法：链脲佐菌素诱导糖尿病小鼠，高糖刺激血管内皮细胞(VECs)和血管平滑肌细胞(VSMCs)。在体外和体内施用MPD以验证其对DMED的功效。c-Myc和AKAP12的相互作用通过荧光素酶报告基因测定和染色质免疫沉淀测定来确定。
结果:c-Myc和AKAP12在DMED小鼠的阴茎组织中上调。在高葡萄糖刺激的VSMC或VEC中，MPD干预增强细胞活力，抑制细胞凋亡，c-Myc和AKAP12降低，p-eNOSSer1177升高。MPD诱导的细胞凋亡抑制，AKAP12的过表达逆转了AKAP12的减少和p-eN0SSer1177的升高。c-Myc作为AKAP12的正调节因子发挥作用。c-Myc的过表达在体外逆转了MPD诱导的效应,通过AKAP12沉默中和。MPD通过抑制AKAP12改善糖尿病小鼠的勃起功能。
结论：MPD通过调节c-Myc/AKAP12通路改善链脲佐菌素引起的糖尿病小鼠的勃起功能障碍，这表明MPD可以被开发为治疗DMED的有前途的天然药物。
方法：链脲佐菌素诱导糖尿病小鼠，高糖刺激血管内皮细胞(VECs)和血管平滑肌细胞(VSMCs)。在体外和体内施用MPD以验证其对DMED的功效。c-Myc和AKAP12的相互作用通过荧光素酶报告基因测定和染色质免疫沉淀测定来确定。
结果:c-Myc和AKAP12在DMED小鼠的阴茎组织中上调。在高葡萄糖刺激的VSMC或VEC中，MPD干预增强细胞活力，抑制细胞凋亡，c-Myc和AKAP12降低，p-eNOSSer1177升高。MPD诱导的细胞凋亡抑制，AKAP12的过表达逆转了AKAP12的减少和p-eN0SSer1177的升高。c-Myc作为AKAP12的正调节因子发挥作用。c-Myc的过表达在体外逆转了MPD诱导的效应,通过AKAP12沉默中和。MPD通过抑制AKAP12改善糖尿病小鼠的勃起功能。
结论：MPD通过调节c-Myc/AKAP12通路改善链脲佐菌素引起的糖尿病小鼠的勃起功能障碍，这表明MPD可以被开发为治疗DMED的有前途的天然药物。
