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| 淫羊藿次苷Ⅱ衍生物YS10治疗勃起功能障碍的作用及机制研究 |
| 朱亮,蔡启亮,辛钟成,牛远杰,陈业刚 |
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| 天津医科大学第二医院天津 300211;天津医科大学总医院天津300211 |
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| 摘要: |
| 目的:研究淫羊藿次苷Ⅱ衍生物YS10治疗勃起功能障碍中的作用和可能的分子机制。方法:将40只SD雄性大鼠随机分为4组:正常组(sham组)，海绵体神经夹伤组(BCNI组)，海绵体神经夹伤-脱水淫羊藿素治疗组(ICAⅡ组)，海绵体神经夹伤-YS10治疗组(YS10组)，每组10只。ICAⅡ组及YS10组分别灌胃2.5 mg/(kg·d)对应溶剂，其余组灌胃等量生理盐水。4周后测定四组大鼠茎海绵体内压(ICP)、平均动脉压(MAP)及ICPmax/MAP值评价勃起功能，Masson、HE及透射电镜实验鉴定阴茎组织内皮细胞形态学变化，Western blot、ELISA检测相关内皮指标，最后验证PI3K/AKT通路。结果:与BCNI组相比，ICAⅡ组及YS10组ICPmax/MAP改善显著具有统计学差异(P ＜0.001)。Masson、HE示YS10治疗后平滑肌萎缩、胶原沉积、内皮和神经功能障碍减轻。透射电镜示ICAⅡ组与YS10组显微结构改善。Western blot示ICAⅡ组及YS10组α-SMA、Calponin1在内皮的表达水平显著高于BCNI组(P ＜0.001)；ELISA示ICAⅡ组及YS10组的n型一氧化氮合酶(eNOS)和e型一氧化氮合酶(eNOS)水平较BCNI组呈升高(P ＜0.001)；此外，ICAⅡ组与YS10组PI3K、p-AKT/AKT表达均较BCNI组显著增加(P ＜0.01)。结论:ICAⅡ、YS10可以修复阴茎海绵体平滑肌/胶原纤维比例失调，改善病理结构，PI3K/AKT信号通路可能在YS10和ICAⅡ恢复阴茎勃起功能中发挥作用。 |
| 关键词: 勃起功能障碍 淫羊藿次苷Ⅱ 一氧化氮合酶 PI3K/AKT 信号通路 海绵体神经损伤 |
| DOI：10.3969/j.issn.1007-6948.2024.06.001 |
| 投稿时间：2024-05-12 |
| 基金项目:天津市卫健委一般项目(2021171) |
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| Actions and mechanisms of icariside Ⅱ derivative YS10 in the treatment of erectile dysfunction |
| ZHU Liang,CAI Qi-liang,XIN Zhong-cheng |
| Department of Urology, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin (300211), China |
| Abstract: |
| Objective To clarify the therapeutic role of icariside Ⅱ(ICA Ⅱ) derivative YS10 in erectile dysfunction, as well as to investigate the possible molecular mechanisms. Methods 40 SD male rats were randomly divided into 4 groups: sham group, BCNI group, ICAⅡ group and YS10 group, 10 rats in each group. ICAⅡ and YS10 groups were given 2.5 mg/(kg·d) of the corresponding solvent by gavage, and the rest of the groups were given equal doses of saline. ICP, MAP and ICPmax/MAP values were measured after 4 weeks to evaluate the erectile function of rats respectively. Masson, HE and transmission electron microscopy experiments were performed to identify the morphological changes of endothelial cells. Western blotting and ELISA were performed to detect relevant endothelial indexes. Finally, the PI3K/AKT pathway was verified. Results Compared with BCNI group, ICAⅡ group and YS10 group showed statistical difference in ICPmax/MAP (P <0.001). Masson and HE showed that smooth muscle atrophy, collagen deposition, endothelial and neurological dysfunction were reduced. Transmission electron microscopy showed that the microstructure of ICAⅡ group and YS10 group was significantly improved. Western blotting showed that the expression levels of α-SMA and Calponin1 in the endothelium of ICAⅡ group and YS10 group were significantly higher than that in the BCNI group (P <0.05); ELISA showed that the eNOS and nNOS level of ICAⅡ and YS10 groups were higher than BCNI group. The expression of PI3K and p-AKT/AKT was significantly increased in ICAⅡ and YS10 groups (P <0.05).Conclusion ICAⅡ and YS10 can repair the disproportionate smooth muscle/collagen fibre ratio of penile corpus cavernosum and improve the pathological structure, YS10 may be superior to ICAⅡ in improving penile erectile function, and the PI3K/AKT signalling pathway may play an important role in restoring the penile erectile function by YS10 and ICAⅡ. |
| Key words: Erectile dysfunction icariside Ⅱ nitric oxide synthase PI3K/AKT signalling pathway cavernous nerve injury |
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