Methylation Of ENOS In Rat Penile Corpus Cavernosum Under Different Pathological States And Its Relationship With Erectile Function

Objective: To clarify the effects of diabetes and hypo-androgen status on the methylation level in penile cavernous tissue and the promoter region e NOS gene,as well as their relationship with erectile function.Methods: 58 eight-week-old male Sprague–Dawley rats were randomly selected into six groups(n=6): the sham operation group(SHAM),the castration group(CAST),the castration + testosterone(CAST+T)group,the normoglycemia group,the diabetic group,and the diabetic+methyltransferase inhibitors(5-aza-dc,1.5 mg/kg)group.Four and six weeks later,the ratio of the maximum intracavernous pressure/the mean arterial pressure(ICPmax/MAP),serum testosterone,the concentration of nitric oxide(NO),expression of DNMT1,DNMT3 a,DNMT3b,e NOS,and the methylation level of e NOS promoter region in rat penile corpus cavernosum had been examed.Results: There were no notable differences in body weight between the sham-operated,castration,and the castration + testosterone replacement rats(SHAM: 321.75±8.27 g,CAST: 330.99±7.30 g,CAST+T: 330.41±3.89g).Body weight of rats in the diabetic group and diabetic + methylation inhibitor group(DM: 291.39±11.10 g,DM+5-AZA: 290.96±4.12g)were significantly lower(NC: 313.22±14.55g)compared to the normoglycemic group(P<0.05);ICPmax/MAP(0.41±0.02)was significantly lower in the castrationn rats compared with the sham-operated group(0.69±0.02)and the castration +testosterone replacement group(0.72±0.01)(P<0.01);ICPmax/MAP in the diabetic rats(0.34±0.02)and the methylation inhibitor group(0.46±0.02)were significantly lower(P<0.01)than the MAP(0.34±0.02)in the normoglycemic group(0.63±0.01)(P<0.001).NO levels were significantly lower in the castration group of rats(CAST: 5.74±0.95 umol/gprot)compared with sham-operated and castration + testosterone rats(SHAM: 11.47±1.33umol/gprot,CAST+T: 11.03±2.40 umol/gprot)(P<0.01).Rats in the diabetic group(DM: 6.90± 0.61 umol/gprot)NO levels were significantly lower compared to the normoglycemic group(NC: 13.44±2.63 umol/gprot)and the methylation inhibitor group(NC: 10.04±2.40 umol/gprot)(P<0.05).Serum testosterone(CAST: 1.0±0.16 nmol/l)was notable decreased in the castrated group rats compared with the sham-operated and testosterone replacement groups(SHAM: 19.03±0.12 nmol/l,CAST+T: 19.16±0.02 nmol/l)(P<0.01).Serum testosterone in the normoglycemic,diabetic and methylation inhibitor groups(NC: 19.56±0.48 nmol/l,DM: 11.67±7.37 nmol/l,DM+5-AZA:13.56±7.99 nmol/l)were not significantly different(P>0.05).The expression of DNMT1,DNMT3 a,DNMT3b,and e NOS in the penile cavernous tissue of rats in the castration group was significantly lower compared with sham-operated and testosterone replacement rats(P<0.05).The expression of DNMT1,DNMT3 a and DNMT3 b in penile cavernous tissue of diabetic rats was big increased compared with normoglycemic rats and methylation inhibitor rats(P<0.05),and the expression of e NOS were significantly reduced in the diabetic group compared with the normoglycemic and methylation inhibitor groups(P<0.001).The methylation level of e NOS promoter region was no big differences in the sham operation group,the castration group,the castration +testosterone group.The methylation level of e NOS promoter region in penile cavernous tissue was significantly higher in the diabetic group compared with the normoglycemic and methylation inhibitor rats(P<0.05).Conclusion: Although low androgen status inhibited the level of methyltransferase in rat penile cavernous tissue,did not affect the level of methylation in promoter region of e NOS.Hyperglycemia inhibits the NO level in the penile cavernous tissue and the erectile function of rats by upregulate the methyltransferase level in the penile cavernous tissue and the methylation level in promoter region of e NOS.Methylation inhibitors can partly improve erectile function in diabetes rats.