〔Abstract〕 Objective To investigate the effect of miRNA-22 on cardiomyocyte apoptosis and autophagy under uremic toxin stimulation and to elucidate the underlying mechanisms of this process. Methods H9 c2 cells stimulated by indoxyl sulfate(IS) were collected and transfected with mimic-miR-22, anti-miR-22 and LeUCP2 respectively. Flow cytometry was used to analyze the survival of H9 c2 cells, and Western blot was used to analyze the expression of autophagy related proteins LC3 and p62. Results Compared with H9 c2 cells subjected to the control treatment, the number of healthy H9 c2 cells decreased(87.5%vs56.9%,P<0.01), while the number of necrotic and apoptotic cells increased(6.2%vs20.6%, 6.3%vs22.5%,P<0.01) after IS treatment. Treatment with the miR-22 mimics reduced the percentages of necrotic and apoptotic cells(11.0%vs20.6%, 11.0%vs22.5%,P<0.05), while treatment with the miR-22 inhibitors increased the percentages of necrotic and apoptotic cells(38.5%vs20.6%, 40.9%vs22.5%,P<0.01). Western blot analysis showed that H9 c2 cells transfected with miR-22 mimics exhibited a low LC3-Ⅱ-to-LC3-Ⅰ ratio[(1.24±0.15)vs(3.26±0.42),P<0.001]but high p62 protein [(0.92±0.06)vs(0.65±0.05),P<0.05]expression compared with cells transfected with corresponding negative control miRNAs; however, miR-22 inhibitors yielded contrasting results[LC3-Ⅱ/Ⅰratio:(4.53±0.42)vs(3.29±0.40),P<0.01;p62:(0.29±0.04)vs(0.58±0.05),P<0.01]. In addition, LeUCP2 transfection resulted in an increase in p62 expression(P<0.05) and a decrease in LC3-Ⅱ-to-LC3-Ⅰ ratio(P<0.05) in H9 c2 cells exposed to IS or miR-22 inhibitor-transfected H9 c2 cells compared with empty lentivirus vector. Conclusion miR-22 plays an important role in reducing IS induced cardiomyocyte apoptosis and autophagy by targeting UCP2.