Effect Of Estrogen On SIRT1 In Ovariectomized Rats

Backgroud: Estrogen protects women as an “umbrella”.Ovarian failure leads to lower levels of estrogen, the organs and tissues of body lose the protection from effect of estrogen after women entering menopause.The progress of aging begins to be accelerated. The decline of estrogen in body promotes the occurrence and development of cardiovascular and cerebrovascular diseases, senile dementia and metabolic syndrome in elderly patients with chronic diseases.Numerous studies have been demonstrated that exogenous estrogen given in postmenopausal women has a protective effect on the organs and tissues to delay the aging.Silent information regulator 2 enzymes of 1(SIRT1) is a highly conserved on nicotinamide adenine dinucleotide(NAD+) deacetylase, known as anti-aging enzyme, with the acetylation and deacetylation role in different histone and non histone to maintain genome stabilityand the energy metabolism to delay the aging of body.Objective:In this study,we established the menopausal model by bilateral ovariectomy and observed the influence on the level of SIRT1 in ovariectomized menopause rats from exogenous estrogen,to further explore the anti-aging mechanism of estrogen.Methods:Thirty-three three-month-old female Sprague-Dawley(SD)rats were selected and randomly divided into sham-operated(Sham,n=11),ovariectomized(OVX,n=11),ovariectomized treated with estradiol(Treated,n=11).Bilateral ovariectomy was performed of rats to establish the menopause models in the group ofOVX and Treated.The Sham group was removed the equal abdominal fat tissue. The treated was given estradiol valerate(E2,0.21mg/kg) suspension by intragastric administration,and the Sham group and OVX group was given the equal physiological saline.Treatment was given once a day for 12 weeks.The follicle stimulating hormone(FSH) and estradiol(E2)was detected by enzyme-linked immunosorbent assay(ELISA)in the rats blood after 12 weeks.The Heart,liver and brain were removed after the rats were sacrificed. SIRT1 expression in these tissues of rats was analyzed by reverse transcriptional polymerase chain reaction(RT-PCR)and ELISA. The expression level of SIRT1 was statistical analysis and comparison between each groups.Results:After the rats were administrated for 12 weeks,FSH levels in OVX group resulted in a siginificant increase compared to the sham and treated groups(P<0.001),the level of E2 were higher than the sham and treated groups(P<0.001).Compared to the ovariectomized groups,The levels of SIRT1 protein and mRNA were significant increased in the treatment group(P<0.05)and higher in the Sham group in the heart,liver and brain tissues of rats. There is no difference in the Treated and Sham group.The levels of SIRT1 protein were significant higher in the heart than liver and brain in the treatment group(P<0.05). However,the SIRT1 protein levels in the liver were siginificantly higher than brain tissues(P<0.05). In the OVX groups,the levels of SIRT1 protein in the heart and liver were higher compared to the brain tissues. There is no statistical differences between heart and liver. In three groups,the level of SIRT1 mRNA in the heart and brain were lower than in the liver tissues.Conclusion:Estrogen can significantly improve the SIRT1 protein and mRNA levels in the ovariectomized rats to delay senescence.