The Effects Of 17β-Oestradiol On The Nervous System In Ovariectomized Rats

Objective:Investigating the effects of exogenous estrogen on the expression of nuclear transcription factor (Nrf2)、heme oxygenase-1 (HO-1)、silent information regulator 1 (SIRT1), and the changes of the neuronal morphology and volume in the hippocampus and cortex of those ovariectomized rats, so as to explore the beneficial effects of estrogen on the nervous system.Method:Forty femal Sprague-Dawley (SD) rats aged three months were randomly divided into four groups as follows:①control group (CON),②sham operation group (SHAM),③ovariectomized group (OVX),④treated group (OVX+E2),10 rats in each group. The OVX+E2 group were treated with 17β-oestradiol 0.2mg/(kg-d) intragastric administration, the other groups were given an equal volume of saline daily. After 16 weeks of treatment, the follicle stimulating hormone (FSH) and estradiol (E2) level in serum from the abdominal aortic blood were measured by enzyme-linked immunosorbent assay (ELISA); weighing the brain mass by electronic balance and calculation of brain mass/body weigh ratio; the Nrf2/HO-1 and SIRT1 protein expression in the hippocampus and cortex were detected by immunohistochemistry and Western blot method.At the same time, the morphology and number of neurons from cerebral cortex and hippocampus region were observed respectively with optical microscope and Nissl staining method.Results:1. The level of FSH in the OVX group was higher than that in SHAM group and OVX+E2 group, and the E2 level was lower than that in SHAM group and OVX+E2group, and there were significant differences(P<0.05).2. There was no statistical difference in the brain mass of rats in each group, while the brain mass/body weigh ratio of the OVX group was lower than that of SHAM group and OVX+E2 group, and there was statistical difference(P<0.05).3. Immunohistochemistry and Western blot results showed that Nrf2 level in hippocampus and cortex of the OVX group rats was higher than in the SHAM group, while lower than that in OVX+E2 group; The level of HO-1 in hippocampus and cortex of the OVX group rats was higher than the SHAM group and OVX+E2 group; The level of SIRT1 in hippocampus and cortex of the OVX group was reduced than the SHAM group and the OVX+E2 group,. And there were statistical difference(P<0.05).4. Pathological results showed that there were no significant differences in the number and arrangement of neurons in the hippocampus and cortical tissue between the SHAM group and the OVX+E2 group, while in the OVX group the number of hippocampal and cortical cells decreased, and the arrangement of neurons disordered.Conclusions:Exogenous estrogen down regulated the expression of HO-1 and increased the expression of Nrf2 and SIRT1 of ovariectomized rats. Meanwhile the brain weight/body weight radio and the normal neuron number and structure in ovariectomized rats were maintained attributing to the exogenous estrogen.