Perimenopause And Parkinson's Disease Regulation Of Estrogen Level On Nogo-A Protein Expression

Objective:In this study,Immunohistology and Western blot were used to detect the changes of estrogen and Nogo-A protein expression in striatum of perimenopausal rats and Parkinson's disease rats.By studying the regulatory effect of Estrogen expression on Nogo-A expression,we can provide theoretical basis for the possible mechanism and therapeutic effect of ERT therapy on Parkinson's disease,and provide new evidence for clinical use of ERT therapy in Parkinson's disease.Methods:The first part of the experiment:30 female SD rats were randomly divided into SHAM group,OVX group and OVX+E2 group.The model was established by smear of vaginal exfoliated cells,detection of estrogen level and measurement of wet weight of uterus.The expression of Nogo-A protein,ER?,?and GPRR30 in the CS region of the rat midbrain were detected by IHC and WB.The second part:60 female SD rats were randomly divided into three groups:?1?SHAM group,?2?OVX group,?3?PD group^[1],?4?PD+OVXgroup,?5?PD+OVX+E2 group.Through behavioral induction experiment and WB method,the expression of yrosine hydroxylase protein in CS area of midbrain was detected,and the model was established successfully.WB method was used to detect the expression of Nogo-A protein and ERs in CS region of midbrain.SPSS 21.0 was used to complete the statistical process.Results:The experiment was successful.1.The expression of Nogo-A protein in CS area of OVX group was significantly higher than that in SHAM group?P<0.05?.2.The expression of Nogo-A protein in CS area of OVX+E2 group was lower than that of OVX group?P<0.05?,and there was no significant difference between OVX+E2 group and SHAM group?P>0.05?.3.The expression of ER?and?receptor in CS area of midbrain in OVX group was significantly lower than that in SHAM group?P<0.05?,and the expression of ER?and?receptor in CS area of midbrain in OVX+E2 group was significantly higher than that in OVX group?P<0.05?.There was no significant difference in GPR30 expression between the two groups?P>0.05?.The experiment was successful.?1?1.The expression of TH protein in OVX group was lower than that in SHAM group,but there was no significant difference?P>0.05?,The main effect of OVX group was not obvious.2.The expression of TH protein in PD group was significantly lower than that in SHAM group?P<0.05?,and the main effect of PD was significant?P<0.05?.3.Compared with PD group and OVX group,TH protein expression in PD+OVXgroup decreased significantly?P<0.05?.Ovariectomy can enhance the effect of PD group,and the interaction between them is significant.4.The expression of th protein in PD+OVX+E2group was significantly higher than that in PD+OVX group,OVX group and PD group?P<0.05?.Compared with SHAM group,th protein was not significantly increased,but still had statistical difference?P<0.05?.?2?1.The expression of Nogo-A protein in OVX group was significantly higher than that in SHAM group?P<0.05?,The main effect of OVX group was obvious.2.The expression of Nogo-A protein in PD group was significantly higher than that in SHAM group?P<0.05?,The main effect of PD group was obvious.But there was no significant difference between PD group and OVX group?P>0.05?.3.Compared with PD group and OVX group,the expression of Nogo-A protein in PD+OVX group was significantly increased?P<0.05?.Ovariectomy could enhance the effect of PD group,and the interaction between them was significant.4.The expression of Nogo-A protein in PD+OVX+E2group was lower than that in PD+OVXgroup,OVX group and PD group?P<0.05?.Compared with SHAM group,Nogo-A protein was decreased,but it did not return to the preoperative level?P<0.05?.?3?1.The expression of ER?and?in OVX group was significantly lower than that in SHAM group?P<0.05?.,The main effect of OVX group was obvious.2.The expression of ER?and?in PD group was not significantly higher than that in SHAM group?P>0.05?,The main effect of PD group was not obvious.There was significant difference between PD group and OVX group?P<0.05?.There was no significant difference in ER?and?expression between PD+OVX group and OVX group?P>0.05?,which indicated that there was no difference in ER?and?expression between PD+OVX group and PD+OVX group,There was no significant interaction between them?P>0.05?.4.The expression of ER?and?in PD+OVX+E2 group was significantly higher than that in OVX group and PD+OVX group?P<0.05?,and there was no statistical significance compared with SHAM group and PD group?P>0.05?.The expression of GPR30 had no significant change in the five groups.Conclusion:The first part of the experimental results showed that estrogen withdrawal could increase the expression of Nogo-A and decrease the expression of ER?and ER?in the CS area of the rat midbrain,which could be corrected by Estrogen replacementt therapy.The second part of the experimental results showed that after ovariectomy,TH protein expression in CS area of midbrain was significantly decreased and Nogo-A expression was significantly increased in Parkinson's rats.It was proved that estrogen withdrawal can aggravate the pathological damage of brain and increase the risk of Parkinson's disease.Although the treatment with estrogen supplement has obvious improvement,it has not completely corrected the pathological change to the level of sham group.It is speculated that this may be related to the experimental modeling time and the short time of estrogen supplement treatment.However,the experimental results show that estrogen is beneficial to the prevention and treatment of Parkinson's disease,and the specific mechanism is not clear.In this process,the expression of ER?and ER?decreased significantly,which can be corrected by estrogen supplement therapy.It is speculated that estrogen may participate in this process by regulating the expression of its receptor.