| Objectives: To understand the effect of icariin on erectile dysfunction and its mechanism. The effects of Icariin on intracavernosal pressure (ICP) and NOS mRNA and protein expression were investigated by in vivo and molecular biological study.Methods:Part one: Icariin was isolated from Epimedii herb, and different concentration of icariin were introcavernouse injected (ICI). The ICP elicited by cavernous nerves (CN) electricity stimulation was recorded. Mean systematic arterial blood pressure (MBp) changes were also investigated. Sildenafil and papaverine used as the controls. The nitric oxide syntheses (NOS) inhibitor Nw-Nitro-L-Arginine (L-NNA), and soluble guanylate cyclase inhibitor H-[ 1,2,4] oxadiazolo [4,3,-a] quinoxalin-l-one(ODQ) were used for investigate whether the ICP improvement after icariin (10-4mol/L) ICI was related with the NO-cGMP signal pathway. After 4 weeks oral treatment of icariin (2mg/kg/day), the effects of Icariin on ICP and the expressions of NOS isoforms proteins in rat corpus cavernous (RCC) were measured by immunohistochemistry stain.Part two: Arteriogenic ED rat model was constructed by bilateral internal iliac arteries legation. The ICP changes were checked and NOS activity changes were tested by NOS kit and NOS isoform expression were measured by RT-PCR and Western blot analyses at 3d, 7d, 14d and 28d after legation.Part three: After 4 weeks oral treatment with icariin (5mg/kg/day and 10mg/kg/day) for A-ED rats, the ICP was measured and the expression of nNOS, iNOS and eNOS in RCC was investigated by RT-PCR, Western-blot analyses. NOS activities of different group were also checked with NOS kit.Results:Part one: Icariin, Sildenafil and papaverine could increase ICP/MBp in a dose-depended manner (p<0.01). Icariin and Sildenafil did not influence MBp (p>.05), however, papaverine did significantly influence MBp (p<0.01). EC50 of Icariin, Sildenafil and papaverine on ICP/MBp were 2.23|amol/L, 0.24umol/L and 9.73umol/L, respectively. ODQ and L-NNA significantly decreased ICP improved by Icariin (10-4mol/L) ICI and CN stimulation. NOS isoforms' expression was up regulated after 4 weeks oral treatment of icariin.Part two: After bilateral internal iliac arteries legation, ICP dramatically decreased from 3d to 28 d and NOS activity decreased at 14d and 28d. Although all expression ofNOS isoforms periodly increased shortly after legation, but all isoforms expression finally decreased at 28d.Part three: ICP in A-ED rat model was significantly decreased in mRNA and protein levels compared to normal group (p<0.01), But after oral treatment with Icariin, the ICP and NOS activity were increased significantly (p<0.01), eNOS was increased as well on mRNA as on protein level. nNOS has no obvious changes after treatment, and iNOS only increased after low dosage oral treatment, hence, the ICP improvement had the similar trend with the eNOS expression and NOS activity changes, and eNOS changes might be correlated with ICP recovery.Conclusion: Icariin could enhance the normal rat's penis erection function in a dose-depended manner, which was related with NO-cGMP signal pathway. The decreased expression and activity of NOS was one of the main pathological reasons of Arteriogenic ED model. Long term oral treatment with icariin could partially recover the erectile function by improving the eNOS expression and NOS activity, these results implied that Icariin might have the long-term therapeutic effects on ED. Further study is needed. |
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