Abstract: OBJECTIVE To screen microRNAs(miRNAs) from human umbilical cord blood mesenchymal stem cells-derived exosomes(hUCBMSC-Exos) that can be used to regulate inflammatory processes, and study the effect of ferulic acid(FA) on miRNAs related to inflammation regulation in hUCBMSC-Exos on this basis. METHODS miRNAs in hUCBMSC-Exos and miRNAs related to inflammation regulation were screened from the existing database, and their intersection was taken to obtain candidate miRNA molecular groups related to inflammation regulation in hUCBMSC-Exos. The umbilical cord blood of full-term healthy newborns was taken, and the isolated mononuclear cells were cultured in DMEM/F12 medium to P4 generation cells, and the differentiation of osteogenesis, chondrogenesis and adipogenesis was identified. The experiment included two parts to verify the effect of FA on hUCBMSC-Exos and inflammatory cytokines secreted by hUCBMSCs: ①The identified hUCBMSC-Exos were randomly divided into experimental group and control group. The experimental group was intervened with 2 mg·L^-1FA, and the control group was treated with equal volume PBS solution for 24 h. hUCBMSC-Exos was extracted by ultracentrifugation combined with ultrafiltration, and its morphology was observed by transmission electron microscope. Its characteristic surface markers CD9, CD63 and TSG101 were identified by Western blotting. The concentration of hUCBMSC-Exos was determined by BCA method, and the expression of candidate miRNAs related to inflammation in exosomes of each group was detected by RT-qPCR. ②The hUCBMSCs were randomly divided into experimental group, model group and control group according to the random number table method. The experimental group and model group were cultured in DMEM/F12 medium containing 30 mmo1·L^-1 glucose for 120h to establish the high glucose damaged hUCBMSCs model. The experimental group was treated with 2 mg·L^-1FA. Model group and control group were treated with PBS solution of equal volume. The content of inflammatory factors in supernatant of each group was detected by ELISA kit after 24h culture. RESULTS The 7 miRNAs such as miR-125b, miR-126, miR-145, miR-146a, miR-21, miR-221 and miR-31-5p, which might be highly expressed in hUCBMSC-Exos and were related to the regulation of inflammation, were obtained through the analysis of GEO sequencing data and the screening of literatures. In the experiment, hUCBMSCs were successfully cultured, isolated and identified, and hUCBMSC-Exos was further collected. After culture for 24 h, the concentration of hUCBMSC-Exos in the experimental group was (1.179±0.03)mg·mL^-1, which was significantly higher than that in the control group of (0.881±0.03)mg·mL^-1 (P<0.01). Compared with the control group, some inflammatory regulation-related miRNAs in the experimental group changed significantly, miR-126-3p and miR-146a-5p were significantly increased, while miR-145 and miR-31-5p were significantly decreased, with statistically significant differences(P<0.05). Compared with the model group, hUCBMSCs secretion of IL-1β and MCP-1 were significantly decreased, while IL-10 and M-CSF were significantly increased in the experimental group after 2 mg·L^-1 FA intervention, with statistically significant differences(P<0.05), while there was no statistically significant difference in IL-6 secretion between the two groups. Compared with the control group, the secretion of IL-1β, IL-6 and MCP-1 of hUCBMSCs in model group was significantly increased, and the difference was statistically significant(P<0.05). There was no significant difference in IL-10 and M-CSF secretion between the two groups. CONCLUSION FA may regulate inflammation by mediating inflammation related miRNA: miR-126-3p, miR-146a-5p, miR-145 and miR-31-5p in hUCBMSC-Exos, to further regulates the inflammatory factors secreted by hUCBMSCs and regulates the body’s inflammatory response. This study further confirmed that FA has the potential to regulate inflammation at the level of exosomes. It laid a solid foundation for further research on the regulation of inflammatory response by FA through hUCBMSC-Exos level.