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淫羊藿苷对血管性勃起功能障碍大鼠的治疗效果及机制初探
姚俊成,刘思巧,颜天,王磊,李玉涛,杨祺,窦科*
0
(四川省医学科学院·四川省人民医院辅助生殖医学中心, 成都 610072
*通信作者)
摘要:
目的 观察淫羊藿苷对血管性勃起功能障碍(ED)大鼠的治疗效果,并初步探究其作用机制。方法 采用双侧髂内动脉结扎的方式构建血管性ED大鼠模型,将其随机分为5组,每组10只:模型组(每天1 mL生理盐水灌胃),他达拉非组(按每天0.8 mg/kg的剂量给予他达拉非溶液灌胃),淫羊藿苷低、中、高剂量组(分别按每天20、40、80 mg/kg的剂量给予淫羊藿苷混悬液灌胃)。假手术组(10只)给予每天1 mL生理盐水灌胃。造模4周后,刺激大鼠阴茎海绵体神经,测量最大阴茎海绵体内压(ICPmax),评估大鼠的勃起功能。连续灌胃30 d后取大鼠阴茎海绵体标本,用ELISA法检测各组大鼠阴茎海绵体中α-平滑肌肌动蛋白(α-SMA)、鞘氨醇-1-磷酸(S1P)和鞘氨醇-1-磷酸受体1(S1PR1)的表达水平;采用Masson染色测定大鼠阴茎海绵体组织纤维化情况,计算所采集图像的积分光密度(IOD)。对各组大鼠ICPmax和阴茎海绵体中α-SMA、S1P、S1PR1水平进行线性回归分析。结果 他达拉非组大鼠的ICPmax高于淫羊藿苷低剂量组,低于淫羊藿苷中、高剂量组(P均<0.05)。他达拉非组大鼠阴茎海绵体的Masson染色IOD低于淫羊藿苷低、中剂量组,高于淫羊藿苷高剂量组(P均<0.05)。他达拉非组大鼠阴茎海绵体中α-SMA的表达水平低于淫羊藿苷高剂量组,高于淫羊藿苷低、中剂量组(P均<0.05)。他达拉非组大鼠阴茎海绵体中S1P的表达水平低于淫羊藿苷中、高剂量组(P均<0.05)。他达拉非组大鼠阴茎海绵体中S1PR1表达水平低于淫羊藿苷低、中、高剂量组(P均<0.05)。线性回归分析结果显示,α-SMA、S1P、S1PR1水平和ICPmax之间存在线性关系(P均<0.05)。结论 淫羊藿苷可显著改善血管性ED大鼠的勃起功能,其可能通过调节S1P、S1PR1水平促进血管内皮的新生和稳定,达到改善勃起功能的目的。
关键词:  淫羊藿苷  血管性勃起功能障碍  鞘氨醇-1-磷酸  鞘氨醇-1-磷酸受体1
DOI:10.16781/j.CN31-2187/R.20220109
投稿时间:2022-01-29修订日期:2022-07-01
基金项目:四川省科技厅重点研发项目(2019YTS0195).
Effect and mechanism of icariin on vascular erectile dysfunction in rats
YAO Juncheng,LIU Siqiao,YAN Tian,WANG Lei,LI Yutao,YANG Qi,DOU Ke*
(Department of Assisted Reproductive Medicine Center, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Science, Chengdu 610072, Sichuan, China
*Corresponding author)
Abstract:
Objective To observe the effect of icariin on vascular erectile dysfunction (ED) in rats and explore its mechanism. Methods The vascular ED rat model was established by ligation of bilateral internal iliac arteries. Then, they were randomly divided into 5 groups (n=10): model group (intragastric administration of 1 mL/d normal saline), tadalafil group (intragastric administration of tadalafil solution at a dose of 0.8 mg/kg per day), and low-, middle-, and high-dose icariin groups (intragastric administration of icariin suspension at doses of 20, 40, and 80 mg/kg per day, respectively). The sham operation group (n=10) was given 1 mL/d normal saline intragastrically. After 4 weeks of modeling, the maximum intracavernous pressure (ICPmax) was measured after stimulating the corpus cavernosum nerve of rats to evaluate the erectile function. After continuous intragastric administration for 30 d, the corpus cavernosum of rats was taken, and the levels of α-smooth muscle actin (α-SMA), sphingosine-1-phosphate (S1P), and sphingosine-1-phosphate receptor 1 (S1PR1) in the corpus cavernosum were detected by enzyme-linked immunosorbent assay. The tissue fibrosis of corpus cavernosum was measured by Masson staining, and the integral optical density (IOD) of the collected images was calculated. The relationship between ICPmax and the levels of α-SMA, S1P, and S1PR1 in corpus cavernosum in each group were analyzed by linear regression. Results The ICPmax in the tadalafil group was significantly higher than that in the low-dose icariin group, but significantly lower than that in the middle- and high-dose icariin groups (all P<0.05). The IOD of corpus cavernosum in the tadalafil group was significantly lower than that in the low- and middle-dose groups of icariin, but significantly higher than that in the high-dose icariin group (all P<0.05). The expression level of α-SMA in corpus cavernosum of rats in the tadalafil group was significantly lower than that in the high-dose icariin group, but significantly higher than that in the low- and middle-dose icariin groups (all P<0.05). The expression level of S1P in corpus cavernosum in the tadalafil group was significantly lower than that in the middle- and high-dose icariin groups (both P<0.05). The expression level of S1PR1 in corpus cavernosum in the tadalafil group was significantly lower than that in the low-, middle- and high-dose icariin groups (all P<0.05). Linear regression analysis showed that there were linear regression relationships between α-SMA, S1P, S1PR1 levels and ICPmax (all P<0.05). Conclusion Icariin can significantly improve the erectile function of vascular ED rats. It may improve the erectile function by regulating the levels of S1P and S1PR1 to promote the neogenesis and stability of vascular endothelium.
Key words:  icariin  vascular erectile dysfunction  sphingosine-1-phosphate  sphingosine-1-phosphate receptor 1