Objective:To investigate the effect of hUCMSC-exos on the expression levels of HDAC in different isotypes of RA FLSs, and to elucidate the possible mechanism of hUCMSC-exos on the apoptosis of RA FLSs by regulating HDAC.Methods:hUCMSC and hUCMSC-Exos were isolated and identified. RT-qPCR was used to detect the changes in HDAC mRNA expression levels in FLSs after hUCMSC-Exos intervention, and the most affected HDAC types were identified. Western blot was used to detect the levels of FLS HDAC1 protein and the expression levels of NF-κB p65 and phospho-NF-κB p65 (Ser 536) in the blank control group, hUCMSC group, hUCMSC-Exos group, Trichostatin A (TSA) group and HDAC1 Inhibitor (Pyroxamide) group. To investigate the effects of hUCMSC-Exos on HDAC expression and NF-κB activity in FLSs. Flow cytometry was used to detect the effect of hUCMSC-Exos on the apoptosis of FLSs. ELISA was used to detect the effects of hUCMSC-Exos on the secretion of TNF-α, IL-6, IL-1β and IL-8 by FLSs. Flow cytometry and ELISA were used to detect the apoptosis level and pro-inflammatory cytokine secretion level of RA FLSs in the blank control group, NF-κB Inhibitor (pyrrolidine dithiocarbamate (PDTC) group, hUCMSC-Exos group and PDTC+hUCMSC-Exos co-intervention group. Whether inhibition of NF-κB affects the regulatory effect of hUCMSC-Exos on RA FLSs was further explored. All experimental data conforming to the normal distribution were compared by one-way ANOVA. LSD- t test was used for pin-group comparison, and independent sample t test was used for two-sample comparison. Results:Cultured primary hUCMSC were adherently grown spindle-shaped cells, and hUCMSC-Exos were saucer-shaped membranous vesicles, both of which met the identification criteria. hUCMSC-Exos reduced the expression level of HDCA1 mRNA [(0.932±0.091), t=2.19, P<0.001] and protein [(0.204±0.012), t=8.28, P<0.001] in RA FLSs, and the inhibitory effect was stronger than that of hUCMSC ( t=1.09, P=0.009) and HDAC1 ( t=11.29, P=0.013) Inhibitor. hUCMSC-Exos increased the apoptosis rate of RA FLSs [(48.68±0.84)%, t=12.33, P<0.001]. hUCMSC-Exos reduced the secretion levels of TNF-α [(29.6±1.0)pg/ml, t=10.78, P<0.001], IL-6 [(20.1±0.7)pg/ml, t=7.96, P<0.001], IL-1β [(9.28±0.23)pg/ml, t=6.14, P<0.001] and IL-8 [(108.0±3.8)pg/ml, t=1.21, P<0.001] in the supernatant of RA FLSs. hUCMSC-Exos reduced the expression level of p-NF-κB-p65/NF-κB-p65 in RA FLSs(0.351±0.024, t=17.67, P<0.001), and its inhibitory effect was stronger than that of hUCMSC (0.515±0.064, t=8.07, P=0.009) and HDAC1 inhibitor(0.411±0.033, t=2.44, P=0.04). After use of NF-κB inhibitors, hUCMSC-Exos weakened the promotion of apoptosis of RA FLSs [(29.0±0.5)%, t=10.63, P<0.001] and weakened the inhibitory effect of IL-8 secretion in the supernatant of RA FLSs [(125.5±3.2)pg/ml, t=2.63, P=0.002]. Conclusion:hUCMSC-Exos can mimic maternal cells to effectively inhibit the aberrant expression of HDAC1 in RA FLSs. hUCMSC-Exos may affect the apoptosis of RA FLSs and the secretion of pro-inflammatory cytokines by inhibiting the HDAC1/NF-κB pathway.