A study on the protective mechanism of human adipose mesenchymal stem cell-derived exosomes combined with astragalus polysaccharides against myocardial injury

GUO Cai-ru; LIU Xin-xin; NIU Yu-jie

doi:10.3969/j.issn.1674-3806.2023.12.09

Abstract：Objective To explore the protective mechanism of human adipose mesenchymal stem cell-derived exosomes(Exosome-HADSCs)combined with astragalus polysaccharides(APS)against myocardial injury.Methods Human adipose mesenchymal stem cells(HADSCs)were cultured in vitro,and exosomes were extracted and identified using electron microscopy and Western blot.Control group,Exo group,APS group and Exo+APS group were set up.The effects of Exosome-HADSCs combined with APS on vascular formation and cell migration of human umbilical vein endothelial cells(HUVECs)were analyzed using the angiogenesis test and the scratch test.In the AC16 cardiomyo-cyte injury model,control group,cobalt chloride(CoCl2)group,CoCl2+Exo group,CoCl2+APS group and CoCl2+Exo+APS group were set up to compare the cell survival rate,apoptosis rate and the expression levels of apoptosis-related proteins among all the groups.Results Compared with that in the control group,the number of vascular mesh formation in HUVECs in the Exo+APS group was significantly increased(P＜0.05),and the number of vascular mesh formation in the Exo+APS group was larger than that in the Exo group and the APS group,and the differences were statistically significant(P＜0.05).Compared with that in the control group,the cell migration rate in the Exo+APS group was increased,and the cell migration rate in the Exo+APS group was higher than that in the Exo group and the APS group,and the differences were statistically significant(P＜0.05).Exosome-HADSCs combined with APS could significantly improve the survival rate of AC16 cells damaged by CoCl2 and decrease the apoptosis rate of AC16 cells damaged by CoCl2,and the effects of Exosome-HADSCs combined with APS were more significant than the effects of Exosome-HADSCs and the effects of APS alone(P＜0.05).Compared with those in the CoCl2 group,the expressions of apoptosis-related proteins B-cell lymphoma-2 associated x protein(Bax)and cysteine aspartate specific protease-3(caspase-3)in the CoCl2+Exo+APS group were significantly decreased(P＜0.05),and the expression of anti-apoptotic protein B-cell lymphoma-2(Bcl-2)was significantly increased(P＜0.05),and the expression levels of phosphatidylinositol-3-kinase(PI3K),phosphated phosphatidylinositol-3-kinase(p-PI3K)and serine-threonine kinase(Akt)were signifi-cantly increased(P＜0.05).Conclusion Exosome-HADSCs combined with APS have protective effects on myocardial injury,which may be related to promoting angiogenesis and endothelial cell migration,improving cell survival rate,and reducing myocardial cell apoptosis through PI3K/Akt signaling pathway.