MiR-200a was shown to be upregulated in the corpus cavernosum （CC） of rats with aging-related erectile dysfunction （A-ED） in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included： aged rats with ED （group AE, n = 8）, aged rats with normal erectile function （group AN, n = 8）, and young rats as normal controls （group YN, n = 8）. CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells （CECs） from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKG pathway.
目的：运用Meta分析研究GNB3基因C825T位点多态性与勃起功能障碍的相关性。方法检索Pubmed、Medline、中国期刊网全文数据库（CNKI）、万方数据库和维普中文科技期刊库，按照纳入标准纳入文献，对文献进行资料提取后，运用STATA 12.0软件进行Meta分析。结果共纳入4篇研究，包括969例ED患者和795例对照。采用共显性模型进行Meta分析，结果显示CC基因型较TT基因型与勃起功能障碍发病无显著关联（OR=0.639，95%CI：0.386-1.059，P =0.083）；对不同人群进行亚组分析提示亚组人群CC基因型较TT基因型勃起功能障碍患病风险增加；欧洲人群GNB3基因C825T位点基因多态性与勃起功能障碍无明显关联（CC vs TT， OR=1.043，95%CI：0.602-1.810，P=0.88； CT vs TT，OR=0.989，95%CI：0.568-1.723，P=0.97）。结论亚洲人群GNB3基因CC基因型为勃起功能障碍的危险因素，而在欧洲人群中关联尚不明确。
The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin （65 mg kg-1）-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, p53 and forkhead transcription factor 0 3a （FOXO3a）, superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SI RT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.
Silent information regulator 2-related enzyme 1(SIRT1)is an aging-related protein activated with aging.Herein,we evaluated the role of SIRT1 in aging-related erectile dysfunction.The expression of SIRT1 was modulated in aged Sprague-Dawley rats following intragastric administration of resveratrol(Res;5 mg kg^(-1)),niacinamide(NAM;500 mg kg^(-1))or Res(5 mg kg^(-1))+tadalafil(Tad;phosphodiesterase-5[PDE5]inhibitor;5 mg kg^(-1))for 8 weeks.Then,we determined erectile function by the ratio of intracavernosal pressure(IcP)/mean systemic arterial pressure(MAP).Cavernosal tissues were extracted to evaluate histological changes,cell apoptosis,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP),the superoxide dismutase(SOD)/3,4-methylenedioxyamphetamine(MDA)level,and the expression of SIRT1,p53,and forkhead box O3(FOX03a)using immunohistochemistry,terminal deoxynucleotidyl transferase(TdT)-mediated 2'-deoxyuridine 5'-triphosphate(dUTP)nick-end labeling(TUNEL),enzyme-linked immunosorbent assays,and western blot analysis.Compared with the control,Res treatment significantly improved erectile function,reflected by an increased content of smooth muscle and endothelium,NO/cGMP and SOD activity,and reduced cell apoptosis and MDA levels.The effect of Res was improved by adding Tad.In addition,the protein expression of SIRT1 was increased in the Res group,accompanied by decreased p53 and FOxO3a levels.In addition,inhibition of SIRT1 by NAM treatment resulted in adverse results compared with Res treatment.SIRT1 activation ameliorated aging-related erectile dysfunction,supporting the potential of SIRT1 as a target for erectile dysfunction treatment.
