PMID- 29722337
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20220317
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 131
IP  - 10
DP  - 2018 May 20
TI  - Accelerated Autophagy of Cecal Ligation and Puncture-Induced Myocardial 
      Dysfunction and Its Correlation with Mammalian Target of Rapamycin Pathway in 
      Rats.
PG  - 1185-1190
LID - 10.4103/0366-6999.231522 [doi]
AB  - 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 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. 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 +/- 0.11, 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). CONCLUSIONS: The autophagy process in the 
      myocardium was accelerated in CLP rats, which was closely correlated with the 
      inhibition of the mTOR pathway.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
FAU - Cui, Na
AU  - Cui N
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
FAU - Han, Wen
AU  - Han W
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
FAU - Su, Long-Xiang
AU  - Su LX
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
FAU - Long, Yun
AU  - Long Y
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
FAU - Liu, Da-Wei
AU  - Liu DW
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing 
      100730, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Cecum/injuries
MH  - Echocardiography
MH  - Immunohistochemistry
MH  - Ligation
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Myocardium/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sepsis/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5956769
OTO - NOTNLM
OT  - Autophagy
OT  - Cecal Ligation and Puncture
OT  - Mammalian Target of Rapamycin
OT  - Myocardial Dysfunction
OT  - Sepsis
COIS- There are no conflicts of interest
EDAT- 2018/05/04 06:00
MHDA- 2018/09/25 06:00
PMCR- 2018/05/20
CRDT- 2018/05/04 06:00
PHST- 2018/05/04 06:00 [entrez]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2018/05/20 00:00 [pmc-release]
AID - ChinMedJ_2018_131_10_1185_231522 [pii]
AID - CMJ-131-1185 [pii]
AID - 10.4103/0366-6999.231522 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2018 May 20;131(10):1185-1190. doi: 10.4103/0366-6999.231522.