Granulocyte colony stimulating factor attenuated myocardial apoptosis via Janus kinase 2/signal transducer and activator of transcription signal transduction pathway in rats with coronary microembolization / 中华心血管病杂志
Chinese Journal of Cardiology
; (12): 254-259, 2008.
Article
en Zh
| WPRIM
| ID: wpr-243803
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of granulocyte colony stimulating factor (G-CSF) on myocardial apoptosis following coronary microembolization (CME) and possible role of Janus kinase/singnal transducer and activator of transcription (JAK/STAT) pathway in this process.</p><p><b>METHODS</b>A total of 92 male Sprague Dawley rats were randomized into CME (n = 24), G-CSF (100 microg x kg(-1) x d(-1) i.p. 2 hours post CME for 5 days, n = 24), JAK2 inhibitor AG490 (G-CSF plus AG490, 5 mg x kg(-1) x d(-1) i.p. 2 hours post CME for 5 days, n = 24), all rats received left ventricular injection of homologous microthrombotic particle suspension post clamping the ascending aorta. Sham-operated group (n = 20) served as control. The rats were sacrificed at day 3, 7, 14 and 28 after operation. The myocardial mRNA expressions of Bcl-2, Bax, Fas, FasL and GAPDH which was used as the intercomparison, were evaluated by real time PCR. The ratio of Bcl-2/Bax was compared. The protein expression of Caspase-3, cleaved PARP, t-JAK2, p-JAK2, t-STAT3 and p-STAT3 were detected by western blot. Myocardial apoptosis were examined by TUNEL staining.</p><p><b>RESULTS</b>Compared with Sham rats, the mRNA of Bcl-2, Bax, Fas and FasL significantly increased whereas the ratio of Bcl-2/Bax (0.28 +/- 0.04 vs. 2.98 +/- 0.49) significantly decreased and the protein expression of Caspase-3 (0.762 +/- 0.129 vs. 0.133 +/- 0.027), PARP (0.992 +/- 0.146 vs. 0.386 +/- 0.074) and the myocardial apoptosis index (17.2 +/- 1.9 vs. 1.2 +/- 0.6) significantly increased in CME hearts (all P < 0.05). rhG-CSF significantly attenuated CME induced changes and cotreatment with JAK2 inhibitor AG490 abolished the effects of rhG-CSF. The protein expressions of t-JAK2 and t-STAT3 among the groups were similar. P-JAK2 and p-STAT3 protein expressions were significantly increased in G-CSF group compared to other groups (P < 0.05).</p><p><b>CONCLUSION</b>G-CSF attenuated myocardial apoptosis induced by CME via JAK2/STAT3 pathway.</p>
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Patología
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Farmacología
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Enfermedad de la Arteria Coronaria
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Transducción de Señal
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Factor Estimulante de Colonias de Granulocitos
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Ratas Sprague-Dawley
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Apoptosis
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Embolia por Colesterol
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Modelos Animales de Enfermedad
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Factores de Transcripción STAT
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
Zh
Revista:
Chinese Journal of Cardiology
Año:
2008
Tipo del documento:
Article