Abstract：Objective: To explore the effects of mesenchymal stem cell derived exosomes carrying miR-122a on diabetic cardiomyopathy (DCM) and the related molecular mechanisms. Methods: miR-122a and miR-NC were transfected into isolated mouse bone marrow derived mesenchymal stem cells (BMSC), and BMSC exosomes (BMSC-Exos) were extracted and identified by western blot. Thirty C57/B6 mice were divided into control group, miR-122a group and miR-NC group. In addition to the control group, the miR-122a group and the miR-NC group were treated with high-fat and high-sugar diet combined with STZ to induced DCM model, and then injected with BMSC-Exos-miR-122a and BMSC-Exos-miR-NC through caudal vein, respectively. The control group was intraperitoneally injected with the same amount of sodium citrate buffer. At the end of the experiment, cardiac function indexes of mice in each group were detected. The pathological level of myocardial tissue was detected by HE, the levels of ROS, IL-1β, IL-6 and TNF-α were detected by ELISA, and the protein expression levels of LC3Ⅱ, LC3Ⅰ, Beclin1 and γH2AX in myocardial tissue were detected by western blot. Results: After transfection, compared with BMSC-miR-NC, the expression of miR-122a in BMSC-miR-122a was increased(P<0.05). The extracted BMSC-Exos showed a typical Exo morphology with a particle size of about 100 nm and high expression of exosome marker proteins CD63 and CD81. Compared with the control group, end-diastolic ventricular septal thickness (IVSd), end-diastolic posterior wall thickness (PWd), left ventricular short-axis shortening rate (LVFS), stroke output (SV) and cardiac output (CO) were decreased(P<0.05), while left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs) and left ventricular mass (LVM) were increased(P<0.05), the myocardial structure was disturbed and inflammatory cell infiltration increased, and the levels of ROS, IL-1β, IL-6 and TNF-α in myocardial tissue were increased(P<0.05), the expression levels of LC3Ⅱ/LC3Ⅰ and Beclin1 protein were decreased(P<0.05), while the expression levels of γH2AX protein were increased in miR-NC group(P<0.05). Compared with miR-NC group, IVSd, PWd, LVFS, SV and CO were increased(P<0.05), while LVDd, LVDs and LVM were decreased(P<0.05), the myocardial structure recovered and inflammatory cell infiltration decreased, and the levels of ROS, IL-1β, IL-6 and TNF-α were decreased(P<0.05), LC3Ⅱ/LC3Ⅰ and Beclin1 protein expression levels were increased(P<0.05), while γH2AX protein expression levels were decreased in miR-122a group(P<0.05). Conclusion: DCM can significantly reduce the autophagy level of cardiomyocytes. BMSC-Exos carrying miR-122a can improve disease symptoms in DCM by restoring autophagy levels of cardiomyocytes, reduce inflammatory levels and cell damage.
2023, Vol. 29 
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