Accelerated Autophagy of Cecal Ligation and Puncture-Induced Myocardial Dysfunction and Its Correlation with Mammalian Target of Rapamycin Pathway in Rats / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 1185-1190, 2018.
Artículo
en Inglés
| WPRIM
| ID: wpr-688147
ABSTRACT
<p><b>Background</b>Recent studies have indicated that autophagy is involved in sepsis-induced myocardial dysfunction. This study aimed to investigate the change of autophagy in cecal ligation and puncture (CLP)-induced myocardium dysfunction and its relationship with mammalian target of rapamycin (mTOR) pathway.</p><p><b>Methods</b>Totally, 12 rats were randomly divided into CLP group or sham-operated (SHAM) group. Cardiac tissues were harvested 18 h after CLP or sham operation. Pathology was detected by hematoxylin and eosin staining, cardiac functions by echocardiography, distribution of microtubule-associated protein light chain 3 type II (LC3II) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, phosphorylation of mTOR (p-mTOR), phosphorylation of S6 kinase-1 (PS6K1), and LC3II and p62 expression were measured by western blotting. Pearson's correlation coefficient was used to analyze the correlation of two parameters.</p><p><b>Results</b>The results by pathology and echocardiography revealed that there was obvious myocardial injury in CLP rats (left ventricle ejection fraction SHAM 0.76 ± 0.06 vs. CLP 0.59 ± 0.11, P < 0.01; fractional shortening SHAM 0.51 ± 0.09 vs. CLP 0.37 ± 0.06, P < 0.05). We also found that the autophagy process was elevated by CLP, the ratio of LC3II/LC3I was increased (P < 0.05) while the expression of p62 was decreased (P < 0.05) in the CLP rats, and there were also more autophagosomes and autolysosomes in the CLP rats. Furthermore, the mTOR pathway in CLP myocardium was inhibited when compared with the sham-operated rats; p-mTOR (P < 0.01) and PS6K1 (P < 0.05) were both significantly suppressed following CLP challenge. Interestingly, we found that the mTOR pathway was closely correlated with the autophagy processes. In our study, while p-mTOR in the myocardium was significantly correlated with p62 (r = 0.66, P = 0.02), PS6K1 was significantly positively correlated with p62 (r = 0.70, P = 0.01) and negatively correlated with LC3II (r = -0.71, P = 0.01).</p><p><b>Conclusions</b>The autophagy process in the myocardium was accelerated in CLP rats, which was closely correlated with the inhibition of the mTOR pathway.</p>
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Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fisiología
/
Autofagia
/
Heridas y Lesiones
/
Inmunohistoquímica
/
Ecocardiografía
/
Ciego
/
Ratas Wistar
/
Sepsis
/
Microscopía Electrónica de Transmisión
/
Serina-Treonina Quinasas TOR
Límite:
Animales
Idioma:
Inglés
Revista:
Chinese Medical Journal
Año:
2018
Tipo del documento:
Artículo
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