| Objective:To investigate the mechanism of myocardial insulin resistance in chronic heart failure (CHF) by observing the influence of androgen on myocardial apoptosis, insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) in CHF rat models, so as to offer new approaches for CHF treatment.Methods:A total of 120 SD male rats with an average age of 7 weeks, weighted (230 ± 20) g were enrolled in this study. They were randomly divided into sham operation group (A), castrated group (B), heart failure (HF) group (C), castrated+HF group (D) and castrated+HF+testosterone replacement therapy group (E). There were 20 rats in group A while 25 rats in other groups. Castration operation was performed on groups B, D and E, and testosterone replacement therapy was applied to group E. Groups C, D and E were treated with doxorubicin hydrochloride to prepare CHF model. Before and after experiment, fasting blood glucose (FPG) and fasting insulin (FIS) levels were measured and thereby insulin sensitivity index (ISI) was calculated. Additionally, echocardiography was performed and left ventricular end diastolic diameter (LVDd), left ventricular end systolic diameter (LVDs), left ventricular end diastolic ventricular interventricular septal thickness (IVS), left ventricular posterior wall thickness (PW), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) were detected. Ejection fraction (EF), left ventricular fractional shortening (FS) and left ventricular weight (LVM) were calculated according to the Devereux formula. After data measurement, the rats were sacrificed and venous blood was collected for plasma testosterone level test. At the same time, myocardial tissue of the left ventricle was used for apoptosis index detecting of apoptotic cells in situ end-labeling (Tunel method). The expression levels of myocardial IR and myocardial IRS-1 were measured by quantitative RT-PCR. Statistical analyses were performed using SPSS software finally.Results:(1) Multiple comparisons showed that there were no differences in the five groups in FPG, FIS, ISI and echocardiography indexes (EF, FS, LVM) before The experiment.(2) After experiment,20 rats in group A,24 rats in group B,20 rats in group C,18 rats in group D and 22 rats in group E survived.(3) After experiment, ISI in groups B, C, D and E all reduced while compared with that of group A, and there were statistically significant differences (P<0.01). Compared with group B, ISI in groups C and D significantly decreased (P<0.05), whereas no statistical significance was found in group E (P>0.05). Compared with group C, ISI in group D decreased (P<0.05) while no significant difference was found in group E (P>0.05). ISI in group E increased while compared with that of group D (P<0.01).(4) After experiment, testosterone levels in groups B, C, D and E all reduced while compared with that of group A, and there were statistically significant differences (P< 0.01). Compared with group B, testosterone levels in groups C and E increased while in group D decreased (P<0.01). Compared with group C, testosterone level in group D decreased (P<0.01) whereas no significant difference was found in group E (P>0.05). Compared with D group, testosterone level in group E significantly increased (P<0.01).(5) After experiment, myocardial IR expression levels in groups B, C, D and E significantly increased while compared with that of group A (P<0.01). Compared with group B, myocardial IR expression level in group D (P<0.01) increased whereas no significant differences were found in group C and group E (P>0.05). Compared with group C, myocardial IR expression level in group D (P<0.01) increased while no statistically significant difference was found in group E (P>0.05). Compared with group D, myocardial IR expression level in group E decreased significantly (P<0.01).(6) After experiment, myocardial IRS-1 expression levels in group D and group E increased significantly (P<0.05) and no significant differences were found in groups B and C while compared with that of group A. Compared with group B, myocardial IRS-1 expression levels in groups D and E increased (P<0.01) while no statistically significant difference was found in group C (P>0.05). Compared with group C, myocardial IRS-1 expression level in group D (P<0.01) increased and no statistically significant difference was found in group E (P>0.05). Compared with group D, myocardial IRS-1 expression level in group E decreased (P<0.01).(7) After experiment, myocardial apoptosis indexes in group C, D and E all increased while compared with that of group A(P<0.01), whereas no difference was found in group B (P>0.05). Compared with group B, myocardial apoptosis indexes of groups C, D and E all increased (P<0.01). Compared with group C, myocardial apoptosis index in group D increased (P<0.01) while no statistically significant difference was found in group E (P> 0.05). Compared with group D, myocardial apoptosis index in group E decreased significantly (P<0.01).Conclusions:(1) The expression level of testosterone reduced and ISI decreased in CHF.(2) Myocardial IR expression level increased and insulin resistance existed in CHF.(3) Insulin resistance in CHF could induce myocardial apoptosis.(4) Androgen supplementation could reduced insulin resistance and affect the expression of IR and IRS-1 in CHF, thereby, reducing myocardial apoptosis and improving cardiac function. |
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