Background：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 myoc...Background：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.Methods：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 ofmicrotubule-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.Results：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.l l,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 CLE 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 PS6K 1 （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 LC31I （r =-0.71,P =0.01）.Conclusions：The autophagy process in the myocardium was accelerated in CLP rats,which was closely correlated with the inhibition of the mTOR pathway.展开更多
基金The work was supported by a grant of the National Natural Science Foundation of China （No. 81601657）.
文摘Background：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.Methods：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 ofmicrotubule-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.Results：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.l l,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 CLE 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 PS6K 1 （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 LC31I （r =-0.71,P =0.01）.Conclusions：The autophagy process in the myocardium was accelerated in CLP rats,which was closely correlated with the inhibition of the mTOR pathway.
