Xenon post-conditioning protects against spinal cord ischemia-reperfusion injury in rats by downregulating mTOR pathway and inhibiting endoplasmic reticulum stress-induced neuronal apoptosis.
10.12122/j.issn.1673-4254.2022.08.20
- Author:
Lan LUO
1
;
Jia Qi TONG
1
;
Lu LI
1
;
Mu JIN
1
Author Information
1. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
apoptosis;
endoplasmic reticulum stress;
mTOR;
spinal cord ischemia/reperfusion injury;
xenon post-conditioning
- MeSH:
Animals;
Apoptosis;
Caspase 3/metabolism*;
Endoplasmic Reticulum Stress;
Endoribonucleases/pharmacology*;
Injections, Intraperitoneal;
Male;
Neurons/pathology*;
Nitrogen/metabolism*;
Oxygen/metabolism*;
Protein Serine-Threonine Kinases;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
RNA, Messenger/metabolism*;
Random Allocation;
Rats;
Rats, Sprague-Dawley;
Reperfusion Injury/metabolism*;
Sirolimus/pharmacology*;
Spinal Cord Ischemia/pathology*;
TOR Serine-Threonine Kinases/metabolism*;
Xenon/therapeutic use*;
bcl-2-Associated X Protein/metabolism*
- From:
Journal of Southern Medical University
2022;42(8):1256-1262
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury.
METHODS:Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord.
RESULTS:The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01).
CONCLUSION:By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.
