Study On Anti-aging Effects And Mechanism Of Phytoestrogens

BackgroundAlzheimer's disease(AD)is clinically a degenerative disease of the central nervous system that occultes onset and progresses progressively.There are currently some hypotheses that attempt to demonstrate its intrinsic The pathogenesis,but the specific cause of the disease is still not clear.The clinical manifestations of the disease are mainly patients with learning and memory dysfunction,loss of recognition,loss of use,and visual space skill impairment,etc.,occur mostly in the elderly,female patients about 2 times more than men,consider female postmenopausal women in vivo Hormone decline is one of the main factors.At present,there are still no ideal therapeutic drugs and treatment methods for Alzheimer's disease in clinic,and they can only try to delay the progression of the disease.Estrogen replacement treatment(ERT)has been used as an important method to prevent and treat postmenopausal women with Alzheimer's disease(AD).It can effectively delay the occurrence of some Alzheimer disease and effectively reduce the risk of morbidity in the population.Sex.However,due to certain obvious side effects of the therapy,for example,the risk of endometrial cancer,breast cancer and other diseases during the use of the patient is increased,and the corresponding clinical application has been greatly restricted.Some researchers in a recent study have found that phytoestrogens have a certain influence on the learning and memory function of the central nervous system,mainly due to the fact that phytoestrogen contains heterocyclic polyphenols with some weak estrogenic activity,but the specific mechanism of action Not yet fully elucidated,remains to be explored.ObjectiveThis project aims to model the effects of aging and learning and memory impairment caused by estrogen reduction in ovariectomized adult female SD rats,using phytoestrogens as the treatment group and estrogen therapy group,and sham surgery.Group and simple castration group were compared between groups,Y-maze test was used to test and analyze the effect of different drugs on the spatial learning and memory ability of female rats after surgery in each group,and the effects of ovariectomy on learning and memory ability of rats were observed.Test the efficacy of phytoestrogen and explore the basic mechanism of action of the drug.The specific expression of doublecortin(DCX)in rat hippocampus was detected by immunohistochemistry and Western blotting,and the specific mechanism of phytoestrogen induced changes in learning and memory ability of estrogen was further analyzed.It provides a theoretical basis for the extensive application of phytoestrogens and the treatment,prevention,and related drug development of related diseases.Methods1.Animal model establishment: 48 healthy female SD rats,about 6-8 weeks of age,weighing: 220g-260 g,were randomly divided into 4 groups with 12 random numbers in each group.The first group of purely castrated control group(OVX group),the second group of sham operation group(sham group),the third group of genistein treatment group(Gs group),the fourth group of estradiol benzoate treatment group(EB group).Different groups of animals were given appropriate surgical treatment and drug replacement therapy.2.Monitoring of general physiological indicators of rats: Closely observe and record the general physiological status of rats in each group.Whether the weight of rats in each group changes during the course of drug replacement treatment and the animal feed consumption,the average daily drinking water changes.3.Learning and memory ability testing: After the drug replacement therapy was completed,the spatial learning and memory abilities of SD rats in each group weretested using the Y-maze test.4.The expression of DCX in frozen section of rat hippocampus tissue: The expression of DCX in hippocampus of rats in each group was observed by immunohistochemical method,and the results of immunohistochemical staining were analyzed by image processing and data analysis.5.Expression of DCX in hippocampus of rats: Western blot was used to detect whether the specific expression of DCX in hippocampus of rats in each group was different.Statistical analysis and comparison between different groups.6.Statistical analysis: Statistical analysis software SPSS17.0 was used for data processing and analysis.The aggregated data was analyzed using the one-way analysis of variance method.If the difference is significant,the LSD method can be used to compare each group.The test level is ?<0.05,if P<0.05,the result can be considered statistically significant.Results1.Y maze test results showed that phytoestrogen treatment group(Gs group)spatial learning and memory ability and sham operation group(sham group),estrogen treatment of estradiol benzoate group(EB group)no significant difference,and Compared with the OVX alone group,the number of false positive reactions increased significantly and the difference was statistically significant.2.The results of DCX immunohistochemistry showed that the number of DCX immunoreactive cells in the hippocampal dentate gyrus in the phytoestrogen treatment group(sham group),estrogen-treated estradiol benzoate group(EB group).There was a significant decrease in the number of DCX immunopositive cells in the castrated control group(OVX group),with significant difference.3.Western blot results of DCX in hippocampus of rats in each group: DCX expression was positive in hippocampus of rats in each group,but there was no significant difference between sham group and EB group Obviously,compared with sham group and EB group,the expression of OVX group decreased significantly(P<0.05).Conclusions1.The results of the Y-maze test showed that there was no significant difference in spatial learning and memory ability between sham group and sham group(sham group)and estradiol benzoate group(EB group).Compared with the ovariectomized control group(OVX group),it can be found that the number of wrong reactions in the OVX group was significantly increased with statistically significant differences.2.The results of DCX immunohistochemistry showed that the number of DCX immunoreactive cells in the dentate gyrus of hippocampus in the phytoestrogen drug treatment group(Gs group)was similar to that of the sham group(sham group)and estradiol benzoate group(There was no significant difference in the EB group.The number of DCX immunopositive cells in the OVX group was significantly decreased,and the difference was statistically significant.3.Western blot analysis of DCX in hippocampus of SD rats in each group: DCX was positively expressed in hippocampal tissues in all groups.Compared with sham group and EB group,GX group was more expression than DCs.The difference was not significant;the OVX group compared with sham group,EB group,OVX group expression decreased significantly,the difference was significant(P <0.05).