Effect of irisin on hypoxic-ischemic brain damage in neonatal rats.
- Author:
Xuan-Pei XU
1
;
Ling-Yi HUANG
;
Feng-Yan ZHAO
;
Jun-Jie YING
;
Shi-Ping LI
;
Yan YUE
;
Wen-Xing LI
;
Yi QU
;
De-Zhi MU
Author Information
1. Department of Pediatrics, West China Second University Hospital/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China. quyi712002@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Animals, Newborn;
Apoptosis;
Brain;
Hypoxia-Ischemia, Brain;
Rats;
Rats, Sprague-Dawley
- From:
Chinese Journal of Contemporary Pediatrics
2020;22(1):58-64
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effect and mechanism of action of irisin on hypoxic-ischemic brain damage in neonatal rats.
METHODS:A total of 248 7-day-old Sprague-Dawley rats were randomly divided into a sham-operation group, a model group, and low- and high-dose irisin intervention groups (n=62 each). The rats in the model and irisin intervention groups were given hypoxic treatment after right common carotid artery ligation to establish a model of hypoxic-ischemic brain damage. Those in the sham-operation group were given the separation of the right common carotid artery without ligation or hypoxic treatment. The rats in the high- and low-dose irisin intervention groups were given intracerebroventricular injection of recombinant irisin polypeptide at a dose of 0.30 µg and 0.15 µg respectively. Those in the model and sham-operation groups were given the injection of an equal volume of PBS. The water maze test was used to compare neurological behaviors between groups. TTC staining, hematoxylin-eosin staining and TUNEL staining were used to observe histopathological changes of the brain. Western blot was used to measure the expression of the apoptosis-related molecules cleaved-caspase-3 (CC3), BCL-2 and BAX.
RESULTS:Compared with the sham-operation group, the model group had a significant increase in latency time and a significant reduction in the number of platform crossings (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significant reduction in latency time and a significant increase in the number of platform crossings (P<0.05). Compared with the sham-operation group, the model group had massive infarction in the right hemisphere, with significant increases in karyopyknosis and karyorrhexis. Compared with the model group, the high-dose irisin intervention group had a smaller infarct area of the right hemisphere, with reductions in karyopyknosis and karyorrhexis. The model group had a significantly higher apoptosis rate of cells in the right cerebral cortex and the hippocampus than the sham-operation group. The high-dose irisin intervention group had a significantly lower apoptosis rate than the model group (P<0.05). At 24 and 48 hours after modeling, the sham-operation group had a significantly lower level of CC3 than the model group (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significantly lower level of CC3 and a significantly higher BCL-2/BAX ratio (P<0.05). The low-dose irisin intervention group had similar laboratory markers and histopathological changes of the brain to the model group.
CONCLUSIONS:Irisin can alleviate hypoxic-ischemic brain damage in neonatal rats in a dose-dependent manner, possibly by reducing cell apoptosis in the cerebral cortex and the hippocampus.
