PMID- 28627343
OWN - NLM
STAT- MEDLINE
DCOM- 20181018
LR  - 20181018
IS  - 2095-4352 (Print)
VI  - 29
IP  - 3
DP  - 2017 Mar
TI  - [Study on the role of autophagy in heme oxygenase 1 preventing hepatic 
      ischemia/reperfusion injury in rats].
PG  - 233-238
LID - 10.3760/cma.j.issn.2095-4352.2017.03.008 [doi]
AB  - OBJECTIVE: To identify the role of autopahgy in the protective mechanism of heme 
      oxygenase 1 (HO-1) against hepatic ischemia/reperfusion (I/R) injury. METHODS: 
      Forty healthy male Sprague-Dawley (SD) rats were randomly (random number table) 
      divided into five groups (n = 8 in each group), namely sham group, model group, 
      cobalt protoporphyrin (CoPP) group, zinc protoporphyrin (ZnPP) group and 
      6-amino-3-methylpurine (3-MA) group. Partial hepatic I/R model was established by 
      clamping the pedicles of left and median lobes for 1 hour and reopening for 6 
      hours in rats, and the rats in sham group were only received celiotomp without 
      hepatic I/R. In the CoPP group, CoPP (a HO-1 inducer, 5 mg/kg) was administered 
      i.p 24 hours before I/R. In the ZnPP or 3-MA group, besides pretreatment with 
      CoPP, the rats were given ZnPP (a HO-1 inhibitor, 25 mg/kg) or 3-MA (an autophagy 
      inhibitor, 30 mg/kg) i.p 1 hour before I/R. Serum alanine aminotransferase (ALT) 
      was determined with automatic biochemistry analyzer. The hepatic pathological 
      scores (PS) were determined under light microscope using hematoxylin-eosin (HE) 
      staining. The hepatocyte apoptosis index (AI) was assessed with terminal 
      dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. 
      Autophagosomes in liver tissue were counted under electron microscope. The mRNA 
      expressions of HO-1, caspase-3, Beclin-1 and Atg-5 in the liver were determined 
      by reverse transcription-polymerase chain reaction (RT-PCR). The HO-1 activity 
      was also measured by the generation of bilirubin with the method of double-wave 
      spectrophotometry. RESULTS: Compared with the sham group, the level of serum ALT 
      significantly increased in the I/R group (U/L: 560.3+/-73.6 vs. 49.1+/-13.8, P < 
      0.01), HE staining showed a severe hepatic injury (PS: 12.0+/-2.0 vs. 1.3+/-0.9, P < 
      0.01), TUNEL staining showed a higher hepatocytes apoptosis and the expression of 
      caspase-3 significantly increased [AI: (19.38+/-3.07)% vs. (3.25+/-1.28)%, caspase-3 
      mRNA (2(-DeltaDeltaCt)): 4.62+/-0.40 vs. 1.05+/-0.15, both P < 0.01]. However, there was no 
      significant difference in the expression of HO-1 and the genes associated with 
      autophagy between the two groups. In the CoPP group, the hepatic injury was 
      blunted compared with that in the I/R group [ALT (U/L): 223.3+/-34.4 vs. 
      560.3+/-73.6, PS: 5.6+/-2.3 vs. 12.0+/-2.0, AI: (11.38+/-2.39)% vs. (19.38+/-3.07)%, 
      caspase-3 mRNA (2(-DeltaDeltaCt)): 2.42+/-0.33 vs. 4.62+/-0.40, all P < 0.01]. HO-1 was 
      induced in the CoPP group and autophagy was also increased significantly after 
      I/R when compared with those in the I/R group [HO-1 mRNA (2(-DeltaDeltaCt)): 3.01+/-0.71 
      vs. 1.14+/-0.20, HO-1 activity (pmolxmg(-1)xh(-1)): 259+/-37 vs. 113+/-26, the number 
      of autophagosomes: 8.75+/-0.87 vs. 1.25+/-0.71, Beclin-1 mRNA (2(-DeltaDeltaCt)): 2.85+/-0.28 
      vs. 1.15+/-0.11, Atg-5 mRNA (2(-DeltaDeltaCt)): 2.44+/-0.25 vs. 1.14+/-0.12, all P < 0.01]. In 
      the ZnPP group, the activity of HO-1 was much lower than that in the CoPP group, 
      and as a result autophagy was decreased and liver injury was increased. In the 
      3-MA group, although there was no difference in the activity of HO-1 compared 
      with that in the CoPP group, autophagy was inhibited, and the protective effect 
      of CoPP was eliminated. CONCLUSIONS: HO-1 could regulate the level of autophagy 
      during liver I/R, and in turn autophagy might mediate the protective effects of 
      HO-1 against liver I/R injury.
FAU - Lan, Sheng
AU  - Lan S
AD  - Department of Anesthesiology, Changhai Hospital, Second Military Medical 
      University, Shanghai 200433, China. Corresponding author: Liu Yi, Email: 
      ziboliuyi@yeah.net.
FAU - Li, Jintai
AU  - Li J
FAU - Liu, Yi
AU  - Liu Y
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
JT  - Zhonghua wei zhong bing ji jiu yi xue
JID - 101604552
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Heme Oxygenase-1
MH  - Liver
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury
EDAT- 2017/06/20 06:00
MHDA- 2018/10/20 06:00
CRDT- 2017/06/20 06:00
PHST- 2017/06/20 06:00 [entrez]
PHST- 2017/06/20 06:00 [pubmed]
PHST- 2018/10/20 06:00 [medline]
AID - 10.3760/cma.j.issn.2095-4352.2017.03.008 [doi]
PST - ppublish
SO  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Mar;29(3):233-238. doi: 
      10.3760/cma.j.issn.2095-4352.2017.03.008.