PMID- 29998890
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20240328
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 131
IP  - 14
DP  - 2018 Jul 20
TI  - Effect of Autophagy Inhibition on the Protection of Ischemia Preconditioning 
      against Myocardial Ischemia/Reperfusion Injury in Diabetic Rats.
PG  - 1702-1709
LID - 10.4103/0366-6999.235867 [doi]
AB  - BACKGROUND: Ischemia preconditioning (IPC) remains the most powerful intervention 
      of protection against myocardial ischemia/reperfusion injury (IRI), but diabetes 
      can weaken or eliminate its cardioprotective effect and detailed mechanisms 
      remain unclear. In this study, we aimed to explore whether changes of autophagy 
      in the diabetic condition are attributable to the decreased cardioprotective 
      effect of IPC. METHODS: Sixty diabetic male Sprague-Dawley rats were randomly 
      divided into the control (C), IRI, rapamycin (R), wortmannin (W), rapamycin + IPC 
      (R + IPC), and wortmannin + IPC (W + IPC) groups. The in vivo rat model of 
      myocardial IRI was established by ligaturing and opening the left anterior 
      descending coronary artery via the left thoracotomy. Durations of ischemia and 
      reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 
      min of reperfusion for measuring serum concentrations of troponin I (TnI) and 
      creatine kinase isoenzyme MB (CK-MB) using the enzyme-linked immunosorbent assay. 
      The infarct size was assessed by Evans blue and triphenyltetrazolium chloride 
      staining. The expressions of LC3-II, beclin-1, phosphoinositide 3-kinase (PI3K), 
      mammalian target of rapamycin (mTOR), and P-Akt/Akt ratio in the ischemic 
      myocardium were assessed by Western blotting. RESULTS: Compared to the IRI group, 
      infarct size (56.1% +/- 6.1% vs. 75.4 +/- 7.1%, P < 0.05), serum cTnI (0.61 +/- 0.21 
      vs. 0.95 +/- 0.26 ng/ml, P < 0.05), and CK-MB levels (6.70 +/- 1.25 vs. 11.51 +/- 2.35 
      ng/ml, P < 0.05) obviously decreased in the W + IPC group. Compared with the C 
      group, myocardial expressions of LC3-II (0.46 +/- 0.04 and 0.56 +/- 0.04 vs. 0.36 +/- 
      0.04, P < 0.05) and beclin-1 (0.34 +/- 0.08 and 0.38 +/- 0.07 vs. 0.24 +/- 0.03, P < 
      0.05) evidently increased, and myocardial expressions of mTOR (0.26 +/- 0.08 and 
      0.25 +/- 0.07 vs. 0.38 +/- 0.06, P < 0.05), PI3K (0.29 +/- 0.04 and 0.30 +/- 0.03 vs. 
      0.38 +/- 0.02, P < 0.05), and P-Akt/Akt ratio (0.49 +/- 0.10 and 0.48 +/- 0.06 vs. 0.72 
      +/- 0.07, P < 0.05) markedly decreased in the IRI and R groups, indicating an 
      increased autophagy. Compared with the IRI group, myocardial expression of 
      beclin-1 (0.26 +/- 0.03 vs. 0.34 +/- 0.08, P < 0.05) significantly decreased, and 
      myocardial expressions of mTOR (0.36 +/- 0.04 vs. 0.26 +/- 0.08, P < 0.05), PI3K 
      (0.37 +/- 0.03 vs. 0.29 +/- 0.04, P < 0.05), and P-Akt/Akt ratio (0.68 +/- 0.05 vs. 
      0.49 +/- 0.10, P < 0.05) increased obviously in the W + IPC group, indicating a 
      decreased autophagy. CONCLUSIONS: Increased autophagy in the diabetic myocardium 
      is attributable to decreased cardioprotection of IPC, and autophagy inhibited by 
      activating the PI3K-Akt-mTOR signaling pathway can result in an improved 
      protection of IPC against diabetic myocardial IRI.
FAU - Liu, Ya-Yang
AU  - Liu YY
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Sun, Chao
AU  - Sun C
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Xue, Fu-Shan
AU  - Xue FS
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Yang, Gui-Zhen
AU  - Yang GZ
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Li, Hui-Xian
AU  - Li HX
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Liu, Qing
AU  - Liu Q
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
FAU - Liao, Xu
AU  - Liao X
AD  - Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100041, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Diabetes Mellitus, Experimental
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - *Myocardial Infarction
MH  - *Myocardial Reperfusion Injury
MH  - Phosphatidylinositol 3-Kinases
MH  - Rabbits
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6048915
OTO - NOTNLM
OT  - Autophagy
OT  - Diabetes
OT  - Ischemia Preconditioning
OT  - Ischemia-Reperfusion Injury
COIS- There are no conflicts of interest
EDAT- 2018/07/13 06:00
MHDA- 2018/12/18 06:00
PMCR- 2018/07/20
CRDT- 2018/07/13 06:00
PHST- 2018/07/13 06:00 [entrez]
PHST- 2018/07/13 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/07/20 00:00 [pmc-release]
AID - ChinMedJ_2018_131_14_1702_235867 [pii]
AID - CMJ-131-1702 [pii]
AID - 10.4103/0366-6999.235867 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2018 Jul 20;131(14):1702-1709. doi: 10.4103/0366-6999.235867.