当归红芪超滤物调控组蛋白去乙酰化酶3对心肌细胞衰老的机制研究OACHSSCD

Objective:To investigate the mechanism by which Angelicae Sinensis Radix-Hedysari Radix ultrafiltrate(RAS-RH)regulates histone deacetylase 3(HDAC3)expression to intervene in X-ray-induced senescence of human cardiomyocytes AC16.Methods:AC 16 cells were randomly divided into a normal group,a negative control group(0 Gy X-ray irradiation+0.5 mL of sa-line),a model group(6 Gy X-ray irradiation+0.5 mL of saline),a low-dose RAS-RH group(6 Gy X-ray irradiation+0.5 mL of low-dose drug-containing serum),a medium-dose RAS-RH group(6 Gy X-ray irradiation+0.5 mL of medium-dose drug-containing serum),and a high-dose RAS-RH group(6 Gy X-ray irradiation+0.5 mL of high-dose drug-containing serum).After intervention,cell proliferation,antioxidant capacity,and cellular senescence were evaluated in each group.The expression levels of transforming growth factor-β1(TGF-β1),Smad3,histone deacetylase 3(HDAC3),and p21 were detected.Results:Compared with the negative control group,AC16 cell viability in the model group was significantly decreased(P＜0.01).The protein expression levels of TGF-β1,Smad3,HDAC3,and p21 were significantly upregulated in the model group(P＜0.05).The proportion of senescence-positive cells was significantly increased(P＜0.01),while total antioxidant capacity(TAC)was significantly reduced(P＜0.05).Com-pared with the model group,the expression levels of TGF-β1,Smad3,HDAC3,and p21 were significantly downregulated in the low-,medium-,and high-dose RAS-RH groups(P＜0.05),with the high-dose group showing the most pronounced reduction.Senes-cence-positive staining was markedly decreased in the high-dose group(P＜0.01).TAC was significantly increased in the medium-and high-dose groups(P＜0.05).Conclusion:RAS-RH can attenuate X-ray-induced senescence in AC 16 cells by inhibiting acti-vation of the TGF-β1/Smad3 signaling pathway and downregulating HDAC3 expression.