Based On The VEGF/PI3K/Akt/eNOS Pathway, Explore The Mechanism Of Vascular Endothelial Injury In CUMS Depression Rats And The Protective Mechanism Of Xingpi Jieyu Recipe

Objective:VEGF/PI3K/Akt/eNOS pathway can reflect vascular endothelial injury.This experiment observe aortic VEGF/PI3K/Akt/eNOS pathway protein changes of chronic unpredictable mild stress(CUMS)depression rat model and the effection of Xingpi Jieyu Decoction,to reveal the vascular endothelial damage of depression rat,and to explore the protection mechanism and the VEGF/PI3K/Akt/eNOS regulatory mechanism of Xingpi Jieyu Decoction.Methods:8 weeks male Wistar rats were randomly divided into blank group,model group,western medicine group,Chinese medicine low dose group,Chinese medicine middle dose group,Chinese medicine high dose group,western medicine group;Western medicine using paroxetine,Chinese medicine using Xingpi Jieyu Decoction,CUMS methods is adopted to establish depression rat model,during the period of stress administered orally,assessment of sugar water preference rate test(SPT)and forced swimming test(FST)are taken at 4,8 weekend,Western Blot was used to detect the expression of PI3K and AKT.Immunofluorescence was used to detect the expression of VEGF and eNOS.Lipid metabolism of rats was detected by ELISA.Results:1.Behavioral results:SPT decreased and FST increased in the model group at 4 weeks,which was significantly different from that of the blank group(p<0.05).Compared with the model group,SPT increased and FST decreased in the Chinese medicine low and middle dose groups(p<0.05 or p<0.01).After 8 weeks of stress,SPT decreased and FST increased,which was significantly different from that of the blank group(p<0.01).SPT increased and FST decreased in each Chinese medicine groups and western medicine group(p<0.05 or p<0.01).2.The results of immunofluorescence showed that the expression levels of VEGFA,eNOS and p-eNOS in the model group were significantly decreased at 4 weeks of stress,which was significantly different from that in the blank group(p<0.01).The expression levels of VEGFA,eNOS and p-eNOS in each group of Chinese medicine and western medicine were significantly increased compared with the model group(p<0.05 or p<0.01).At week 8,VEGFA,eNOS,and p-eNOS in the model group decreased significantly compared with the blank group(p<0.01).The expression levels of VEGFA,eNOS and p-eNOS in each group of Chinese medicine and western medicine were significantly increased compared with the model group(p<0.05 or p<0.01).3.Western blot results showed that there was no significant difference in PI3K,Akt,p-Akt between the model group and the blank group at 4 weeks(p>0.05).At 8 weeks,the expression levels of PI3K,Akt and p-Akt in the model group increased significantly,and the differences were significant compared with the blank group(p<0.01).PI3K in each group of Chinese medicine decreased significantly compared with the model group(p<0.01).Akt was significantly decreased in the middle and high dose groups of Chinese medicine,which was significantly different from that in the model group(p<0.05).p-Akt was significantly decreased in each group of Chinese medicine and western medicine,and was significantly different from the model group(p<0.05 or p<0.01).4.ELISA results showed that there were no significant differences in LDL,TG,TC,or HDL between the groups at 4 weeks(P>0.05).At 8 weeks,LDL,TG,TC and HDL were not significantly different(P>0.05).Conclusion:1.The changes of VEGF/PI3K/Akt/eNOS expression levels at week 4 and 8 suggests the vascular endothelial dysfunction in depressed rats and further deterioration with time.2.The preventive administration of Xingpi Jieyu Decoction has a protective effect on vascular endothelial injury in CUMS depression rats,and the effect is more obvious than that of paroxetine.