Role of HIF-1α-glycolytic pathway in propofol-induced attenuation of brain injury in acute sleep-deprived aged rats
10.3760/cma.j.cn131073.20231202.00606
- VernacularTitle:HIF-1α-糖酵解通路在丙泊酚减轻急性睡眠剥夺老龄大鼠脑损伤中的作用
- Author:
Hao QI
1
;
Zhou YOU
;
Yiling LI
;
Wei SHEN
Author Information
1. 武汉科技大学附属孝感医院感染控制科，孝感 432000
- Keywords:
Propofol;
Sleep deprivation;
Brain injuries;
Hypoxia-inducible factor 1α;
Glycolysis
- From:
Chinese Journal of Anesthesiology
2024;44(6):675-681
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of hypoxia-inducible factor 1α (HIF-1α)-glycolytic pathway in propofol-induced attenuation of brain injury in acute sleep-deprived aged rats.Methods:Forty-eight male SPF-grade healthy Sprague-Dawley rats, aged 20-22 weeks, weighing 500-600 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), sleep deprivation group (SD group), sleep deprivation + propofol group (SP group), and sleep deprivation + propofol + DMOG group (SPD group). The sleep deprivation model was developed using a sleep deprivation apparatus in rats. At 20 and 3 h before sleep deprivation, 1% propofol at a dose of 0.04 mg/g was intraperitoneally injected in SP group, and 1% propofol at a dose of 0.04 mg/g and HIF-1α activator DMOG at a dose of 0.05 mg/g were intraperitoneally injected in SPD group. Cognitive function was assessed by fear conditioning test and novel object recognition test. After the behavioral testing, the blood and brain tissue samples were collected for determination of blood-brain barrier permeability (by Evans blue staining), apoptosis rate (by TUNEL staining), serum levels of neurofilament light chain protein (NfL) and neuron-specific enolase (NSE), contents of reactive oxygen species (ROS), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), lactate and pyruvate (by enzyme-linked immunosorbent assay) and expression of HIF-1α, pyruvate kinase M2 (PKM2), hexokinase 2 (HK2), ionized calcium-binding adaptor molecule 1 (IBA1), and cleaved caspase-3 (by Western blot) and for microscopic examination of pathological changes of the hippocampal tissues. The lactate/pyruvate ratio was calculated. Results:Compared to Con group, the percentage of freezing time and recognition index were significantly decreased, serum concentrations of NSE and NfL, EB content in brain tissues, contents of ROS, IL-6 and iNOS in hippocampal tissues, and lactate/pyruvate ratio were increased, the expression of HIF-1α, PKM2, HK2, IBA1 and cleaved caspase-3 was up-regulated, the apoptosis rate was increased ( P<0.05), and the pathological damage to nerve cells in the hippocampus was found in SD group and SPD group. Compared to SD group, the percentage of freezing time and recognition index were significantly increased, serum concentrations of NSE and NfL, EB content in brain tissues, contents of ROS, IL-6 and iNOS in hippocampal tissues, and lactate/pyruvate ratio were decreased, the expression of HIF-1α, PKM2, HK2, IBA1 and cleaved caspase-3 was down-regulated, the apoptosis rate was decreased ( P<0.05), and the pathological damage to nerve cells in the hippocampus was significantly attenuated in SP group. Compared to SP group, the percentage of freezing time and recognition index were significantly decreased, the serum concentrations of NSE and NfL, EB content in brain tissues, contents of ROS, IL-6 and iNOS in hippocampal tissues, and lactate/pyruvate ratio were increased, the expression of HIF-1α, PKM2, HK2, IBA1 and cleaved caspase-3 was up-regulated, the apoptosis rate was increased ( P<0.05), and the pathological damage to nerve cells in the hippocampus was aggravated in SPD group. Conclusions:Propofol can attenuate acute sleep deprivation-induced brain injury in aged rats, and the mechanism may be related to inhibition of the HIF-1α-glycolytic pathway and reduction of neuroinflammatory responses.
