Study On The Mechanism Of Yimai Granules In Treating Vascular Dementia By Regulating Mitochondrial Energy Metabolis

Purpose:Based on mitochondrial energy metabolism,this study explored the effects and mechanism of Yimai granule on mitochondrial fusion and division in hippocampal tissue of gerbil with Vascular dementia,providing scientific basis for the treatment of(VD Vascular dementia).Materials and Methods : Forty-eight healthy male Mongolian gerbils were fed adaptively.Two weeks later,they were randomly divided into sham operation group,model group,yimai granule low-dose group,Yimai granule medium-dose group,Yimai granule high-dose group and Donepezil hydrochloride group,with 8 rats in each group.All groups were free to eat and drink.Except for the sham operation group,the other groups were modeled for ligation and reperfusion of jugular vein,while the sham operation group only exposed jugular vein without ligation and reperfusion and other subsequent steps.On the second day of modeling,both the sham operation group and the model group were fed with the same volume of normal saline,and the yimai granule low-medium-high-dose group and donepezil hydrochloride treatment group were given corresponding drugs and corresponding doses of intragastric intervention.According to the conversion coefficient of human and animal body surface area,the dosage of intragastric drugs was determined.Gavage was performed twice a day,and samples were collected after 28 days of continuous administration.Morris water maze and Y maze were used to test the learning and memory function of gerbils.The morphological changes of hippocampal tissue were observed by HE staining.ATP content in gerbils serum was detected by ELISA.Morphological changes of mitochondria in hippocampal tissue of gerbils were observed by transmission electron microscopy.Western Blot was used to detect the expression of proteins related to mitochondrial fusion lysis.Results:1 Effects of Yimai Granule on learning and memory function of VD gerbilsCompared with sham operation group,the learning and memory ability of model group decreased significantly;Compared with model group,the learning and memory ability of gerbils in all treatment groups was significantly improved,and the treatment effect of Yimai granule medium-dose group and Donepezil hydrochloride group was better(P<0.01,P<0.05).2 Effects of Yimai Granule on morphological changes of neurons in hippocampal CA1 region of VD gerbilsCompared with sham operation group,the number of hippocampal neurons in model group was reduced,with sparse and irregular arrangement,vague cell membrane outline,unclear structure,broken mitochondrial crest,reduced number,reduced fusion and increased division.Compared with the model group,the number of hippocampal neurons in all treatment groups increased significantly,arranged in a more orderly and compact way,with clear and complete cell structure,normal nucleus,normal mitochondrial crest,increased fusion and reduced division.The experimental results showed that yimai granule dose group and donepezil hydrochloride group had the best therapeutic effect.3 Effects of Yimai granules on mitochondrial energy metabolism of VD gerbilsELISA results showed that compared with sham operation group,ATP content in model group decreased(P<0.01,P<0.05);Compared with model group,ATP content in yimai granule treatment group and Donepezil hydrochloride treatment group increased(P<0.01,P<0.05).Western Blot results showed that compared with the sham operation group,the protein expression levels of fusion related proteins Mfn1,Mfn2,Opa1 and energy metabolism-related proteins BDNF and ATP decreased in the model group,while the protein expression levels of fission related proteins Drp1 and Fis1 increased(P<0.01,P<0.05);Compared with model group,protein expression levels of Mfn1,Mfn2,Opa1,BDNF and ATP increased in Yimai granule and Donepezil hydrochloride treatment group,while protein expression levels of Drp1 and Fis1 decreased(P<0.01,P<0.05).Conclusion:1.Yimai granules can improve the learning and memory dysfunction of gerbils.2.Yimai granules can improve the learning and memory dysfunction of VD gerbils by regulating the expression of proteins related to mitochondrial energy metabolism.3.Yimai granules can improve mitochondrial dynamics and regulate energy metabolism,thus promoting the increase of ATP production and restoring energy supply.