ABSTRACT
Objective:To investigate the effect of up regulation of GDF-15 expression on the proliferation,apoptosis and PI3K/AKT signaling pathway of H9C2 cardiomyocytes induced by H2O2.Methods:CCK8 method was used to detect the proliferation of H9C2 cardiomyocytes treated with different concentrations of H2O2;H9C2 cells were divided into Control group,NC group,H2O2group,GDF-15+H2O2group,the cells were treated for 24 h,mRNA and protein expression of GDF-15 in each group were detected by RT-PCR and Western blot;the proliferation and apoptosis of the cells were detected by CCK8 and flow cytometry respectively;DCFH-DA probe was used to detect the level of ROS;the expression of Ki67,Bcl-2,Bax,PI3K and p-AKT protein was detected by Western blot.H9C2 cells were treated with 10 μmol/L LY294002(a PI3K/AKT signal pathway inhibitor),cell viability and apoptosis rate were detected by CCK8 assay and flow cytometryin espectively.Ki67,Bcl-2,Bax,PI3K and p-AKT protein expression were detected by Western blot.Results:Cell viability was inhibited after different concentrations H2O2treated H9C2 myocardial cells,which was concentration de-pendent (P<0.05),due to H9C2 cardiomyocytes treated with 200 μmol/L H2O2inhibited nearly half of cell proliferation,and were chosen as subjects.Compared with control group,mRNA and protein expression of GDF-15 in H2O2group were significantly increased, cell proliferation was decreased significantly,the apoptosis rate was increased,ROS level was increased,the expression of Ki67,Bcl-2, PI3K,p-AKT protein were decreased,Bax protein expression was increased(P<0.05).Compared with H2O2group,mRNA and protein expression of GDF-15 in GDF-15+H2O2group were significantly increased,cell proliferation was significantly increased,the apoptosis rate was decreased,ROS level was decreased,the expression of Ki67,Bcl-2,PI3K,p-AKT protein were increased,and Bax protein expression was decreased (P<0.05).The cell viability and protein expression of Bcl-2,PI3K and p-AKT in PI3K/AKT inhibitor group were significantly lower than those in GDF-15+H2O2group,and the apoptosis rate and Bax protein expression were significantly higher than those in GDF-15+H2O2group(P<0.05).Conclusion:Up regulation of GDF-15 expression promote the proliferation of H9C2 car-diomyocytes induced by H2O2and reduce apoptosis,and the mechanism may be related to the regulation of ROS levels,Ki67,Bcl-2,Bax expression and PI3K/AKT signaling pathway in cells.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze factors influencing the choice of atrial septal occluder (ASO) for transcatheter closure of patients with secundum atrial septal defect (ASD).</p><p><b>METHODS</b>A total of 1114 ASD patients [388 males, aged from 2 to 75 years, mean age (26.3 +/- 17.0) years] were enrolled. Patients were divided to adult (> 14 years, mean 34.4 years, n = 779) and child (< or = 14 years, mean 7.3 years, n = 335) groups. ASD size in different ultrasound cross-sections was determined by transthoracic echocardiography (TTE). ASO size was chosen on the basis of the maximum diameter of the defect (MD). Defect-shapes and rim lengths of ASD, the difference choice of ASO in the two groups were compared.</p><p><b>RESULTS</b>MD of the defects ranged from 5 to 40 mm [mean (19.7 +/- 7.8) mm]. ASD was successfully occluded in 1085 out of 1114 patients (97.4%). Occluder size ranged from 6 to 46 mm [mean (25.8 +/- 8.9) mm] and the difference between occluder size and MD ranged from 2 to 10 mm [mean (6.1 +/- 3.4) mm, ASO/MD ratio 1.3:1]. Though the diameter of the defect was similar between the 2 groups, the size of occluder was significantly larger in adult group than that in child group (ASO/MD ratio 1.1 - 1.6:1 vs. 1.2 - 1.8:1, P < 0.05). MD was significantly correlated with ASO in both groups (r = 0.911 and r = 0.944 in adults and child groups, respectively, all P < 0.01). The size and increment of the occluder used in patients with deficient anterior rims was significantly bigger than patients with sufficient anterior rims (P < 0.01).</p><p><b>CONCLUSION</b>The maximum diameter of the defect was the major determinant for selecting occluder size and choice of occluder size was also influenced by patient age, defect-shape and defect rim for transcatheter closure of secundum ASD.</p>