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.