To analyze the serum exosomal miRNA change in mice with cytoxan induced cardiotoxicity assessed by echocardiography, and then to explore its possibility in evaluating the cytoxan related cardiotoxicity.

C57BL /6 mice aged at 7-8 weeks were randomly divided into two groups, one with control treatment while the other with cytoxan treatment. Cytoxan treated mice were given cyclophosphamide 100 mg /(kg?week), according to the clinical chemotherapy regimen, continuous intraperitoneal injection for 2 weeks, rest 1 week, and then continuous injection for 2 weeks, a total of 5 weeks; Control mice were injected intraperitoneally with an equal volume of 0.9% sodium chloride solution. Five weeks after initial treatment, mice were subjected to echocardiography for cardiac function analysis, maesuring or calculating left ventricular ejection fraction (LVEF), short-axis fractional shortening (FS), left ventricular isovolumic relaxation time (IVRT) and Tei index. Serum exosome isolation were also performed, exosomal miRNA candidates were analyzed by qPCR. The t test was used to compare LVEF, FS, IVRT, Tei index, and serum exosomal miRNA expression levels between the cytoxan treated group and the control group.

Compared with the control mice,cytoxan treated mice had decreased LVEF and FS [0.62±0.05 vs 0.72±0.06, (28.00±3.10)% vs (35.10±4.95)%], and the difference was statistically significant (t=3.591, P=0.003; t=3.453, P=0.004); The Tei index and IVRT were increased [0.71±0.17 vs 0.59±0.14, (27.42±8.42) ms vs (23.40±6.70) ms], but the difference was not statistically significant.Compared with the control mice, the expression of miR-133a-3p and miR-146a-5p in serum exosomes increased in the cytoxan treated group (1.931±1.460 vs 0.072±0.077, 1.895±1.059 vs 0.790±0.296), and the differences were statistically significant (t=4.072, P=0.001; t=3.168, P=0.006); There was no significant difference in the expression of miR-30c-5p and miR-99a-5p (0.870±0.327 vs 0.530±0.670, 0.404±0.134 vs 0.714±0.404).

Cytoxan treatment has an obvious cardiotoxicity in mice, and miR-133a-3p and miR-146a-5p increase. This study suggests that these exosomal miRNAs might serve as a biomarker for cytoxan related cardiotoxicity.