| Objective: The research group has previously demonstrated that icariin improves erection function in SHR rats,and it is not clear whether icariin improves SHR erection by oxidative stress by up-regulating NRF2 and its effect on signaling pathway.NRF2 can oxidize through transcription of many cytoprotective genes.NRF2 and its signaling pathways are important cellular defense mechanisms against antioxidant stress.This study explores whether icariin can regulate the nuclear factor red blood cell 2-related factor 2(Nuclear Factor Erythroid 2–Related Factor 2,NRF2)pathway improves the erectile function of spontaneously hypertensive rats(SHR).Methods: Healthy male WKY rats and healthy male SHR rats were randomly divided into 4 groups(6 in each group,a total of 24): WKY control group(group A: WKY group),WKY + icariin group(group B:WKY treated by icariin group),SHR control group(C group: SHR group),SHR + icariin group(Group D: SHR treated by icariin group).The average weight of each rat is about 300 g,and the age is about 10 weeks.In the breeding animal room,the high-purity extract of epimedium was used to dissolve the icariin in normal saline,and the rats of group B and group D were intragastrically administered at a dose of 10 mg / kg using a stainless steel gavage needle with a length of 9 cm and a needle diameterof 1.6 mm.Groups A and C were treated with normal saline.After 4weeks of regular gavage and control treatment,the serum testosterone levels,average body weight values,the ratio of maximum intracorporeal pressure / average arterial pressure(ICPmax / MAP)of corpora cavernosa,and NRF2,HO-1 in corpora cavernosa were measured,ENOS,p-eNOS,PPAR-γ,DDAH,ADMA and cGMP.The expression of NRF2,HO-1,PPAR-γ,DDAH1,and DDAH2 was determined by immunohistochemistry,and the expression of NRF2,HO-1,ppar-γ,DDAH1,DDAH2,eNOS,and p-eNOS was analyzed by Western blot.Enzyme Linked Immunosorbent Assay(ELISA)was used to detect ADMA and NO levels.Results: After 4 weeks of treatment,the serum testosterone levels of each rat were measured(WKY control group: 485.3 ± 112.3ng / dl,WKY+ icariin group: 299.5 ± 6.5ng / dl,SHR control group: 301.2 ± 5.9ng / dl,SHR + icariin group: 295.3 ± 3.4ng / dl)There was no significant difference between the four groups.Weight average(WKY control group:300.2 ± 3.3g,WKY + icariin group: 299.5 ± 6.5g,SHR control group:301.2 ± 5.9g,SHR + icariin group: 295.3 ± 3.4g)No significant difference.Electrical stimulation of corpus cavernosum in rats measured the ICPmax / MAP ratio,in the WKY control group(3V: 0.27 ± 0.03,5V:0.56 ± 0.02)and the WKY + icariin group(3V: 0.28 ± 0.02,5V: 0.56 ±0.03)There was no significant difference,the SHR control group(3V:0.08 ± 0.04,5V: 0.11 ± 0.03)and the SHR + icariin group(3V: 0.10 ±0.02,5V: 0.21 ± 0.04)were significantly reduced(P <0.05).).Western blot analysis was used to detect the expression of NRF2,HO-1,eNOS,P-eNOS,PPAR-γ,DDAH1,and DDAH2 in SHR cavernous body.Compared with SHR group,NHR2,HO-1,eNOS in SHR + icariin treatment The expression of P-eNOS,PPAR-γ,DDAH1 and DDAH2 increased significantly(p <0.05),and the ratio of P-eNOS / eNOS expression in the SHR + icariin treatment group increased significantly(p<0.05).WKY There was no significant difference between the control group and the WKY + icariin group.Immunohistochemical analysis of NRF2,HO-1,PPAR-γ,DDAH1 and DDAH2 expression in SHR cavernous body Significantly increased(p <0.05),while the expressions of NRF2,HO-1,PPAR-γ,DDAH1,and DDAH2 were not significantly changed in the WKY group and the WKY + icariin treatment group.The cGMP,ADMA and NO concentrations in SHR cavernous bodies were detected by ELISA.The expression of NO and cGMP in the SHR +Icariin treatment group was significantly increased compared with the SHR group(p <0.05),and the expression of ADMA in the SHR + Icariin treatment group was significantly lower than the SHR group(p <0.05).There was no significant change in the expressions of cGMP,ADMA and NO in the WKY group compared with the WKY + icariin treatment group.After measuring the correlation between the expression of NRF2 and the ratio of P-eNOS / eNOS in the cavernous body of the penis,it was found that the expression of NRF2 in the cavernous body waspositively correlated with the level of P-eNOS / eNOS(Y = 0.052 +0.309 X,r = 0.915,p < 0.01).Conclusion: Icariin improves the erectile function of SHR by up-regulating NRF2 expression in rat corpus cavernosum,up-regulating HO-1,DDAH and PPAR-γ,and increasing the ratio of P-eNOS / eNOS. |
