Figure 3.

Silence of the Met gene through AAV9 attenuates crizotinib-induced cardiac complications in vivo. AAV9-TNNT2-si Met or AAV9-TNNT2-NC virus was injected into C57BL/6J mice (n ≥ 9) through the tail vein. Three weeks after injection, mice were then intragastrically administrated with vehicle or 100 mg/kg crizotinib for another 6 weeks. (A) Total protein was extracted from mice hearts (n = 4). Representative immunoblots and relative quantification of the MET were shown. ACTB was used as a loading control. (B-D) the heart function of mice was measured by echocardiography. (E) H&E staining. The yellow arrow indicated typical pathological changes. Scale bar: 40 μm. (F) the cardiac remodeling gene expression relative to Actb was shown. n = 5. (G and H) Representative images of cardiac sections stained by Sirius red or Masson from C57BL/6J mice. Scale bar: 40 μm. (I) TEM observation of the cardiac ventricles from mice (A) and representative images were shown. Scale bar: 1 μm. (J) the mt-Atp6: Rpl13 ratio was measured as a relative mtDNA level. n = 5. Data were presented as mean ± SD. The P value was calculated by one-way ANOVA with Sidak’s test (A, C, D, F and J) multiple comparisons test. ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05. Crizo: crizotinib.