Isoflurane Attenuates Cerebral Ischemia/reperfusion Injury by Improving Mitochondrial Function via Aldose Reductase
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0510
- VernacularTitle:异氟醚通过醛糖还原酶改善线粒体功能保护脑缺血/再灌注损伤
- Author:
Wen JIANG
1
;
Jie LI
2
;
Yan HUANG
2
;
Jing-bo SUN
2
;
Min-zhen DENG
2
;
Yue-fang CAI
1
;
Sookja Kim CHUNG
3
;
Xiao CHENG
2
Author Information
1. The Second Clinical Medical College of Guangzhou University of Chinese Medicine，Guangzhou 510405，China
2. Guangdong Provincial Hospital of Traditional Chinese Medicine // The Second Affiliated Hospital of Guangzhou University of Chinese Medicine，Guangzhou 510006， China
3. Faculty of Medicine， Macau University of Science and Technology， Macau 999078， China
- Publication Type:Journal Article
- Keywords:
isoflurane;
cerebral ischemia/reperfusion injury;
aldose reductase;
mitochondrial function
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(5):721-728
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of Isoflurane （ISO） on the mitochondrial function of Cerebral ischemia/reperfusion （I/R） mice and its possible mechanism. MethodsAldose reductase knockout mice （AR-/-） and control wild-type mice （WT） were randomly divided into WT-S group， WT-IR group， WT-IR+ISO group， AR-/-+S group， AR-/-+IR group， AR-/-+IR+ISO group （Six in each group）. Mice middle cerebral artery embolization model was established by thread embolization method （1 h after ischemia， 23 h after reperfusion）. Zea-Longa method was used to evaluate the neurological function scores of mice. 2，3，5-TTC staining was used to assess the volume of cerebral infarction， Western blot was used to detect AR protein expression in brain tissue， and immunofluorescence localization was used to detect AR protein expression level in ischemic penumbra. TUNEL method was used to evaluate the apoptosis of ischemic penumbra cells， and flow cytometry was used to analyze the opening degree of mitochondrial permeability transition pore （MPTP）. ResultsCerebral ischemia/reperfusion injury caused neurological impairment and cerebral ischemic infarction in mice （P<0.01）. Meanwhile， the expression of AR protein in the ischemic penumbra was up-regulated （P<0.01）， and the apoptosis of brain cells and the opening of mitochondrial MPTP were increased （all P<0.001）. Compared with WT-IR group， neurological function score， cerebral infarction volume， apoptosis and MPTP openness were significantly improved in AR-/-+IR group （all P<0.05）. Compared with WT-IR group， neurological score and cerebral infarction volume were significantly decreased in WT-IR+ISO group （all P<0.05）， AR protein expression in the injured brain tissue was decreased （all P<0.01）， apoptotic cells and MPTP openness in the injured brain tissue were decreased （all P<0.001）. Compared with AR-/-+IR group， AR-/-+IR+ISO group showed no significant difference in neurological function score， cerebral infarction volume， apoptotic cells and MPTP openness. ConclusionIsoflurane can reduce the mitochondrial function injury by reducing the expression of AR protein， thus improving the cerebral ischemia/reperfusion injury in mice.
