Role of AMPK-SIRT1-NF-κB signaling pathway in reduction of brain injury by panax notoginseng saponins in mechanically ventilated rats
10.3760/cma.j.cn131073.20231129.00508
- VernacularTitle:AMPK-SIRT1-NF-κB信号通路在三七总皂苷减轻机械通气大鼠脑损伤中的作用
- Author:
Xinyu XIAO
1
;
Jin ZHANG
;
Aidong GAO
;
Xiuhua LI
;
Qingqiang QIAN
Author Information
1. 唐山市工人医院麻醉科，唐山 063000
- Keywords:
Notoginseng radix et rhizoma;
AMP-activated protein kinase;
Sirtuin 1;
NF-kappa B;
Respiration, artificial;
Brain injuries
- From:
Chinese Journal of Anesthesiology
2024;44(5):568-573
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of the AMP-activated protein kinase (AMPK)-silent information regulator 1 (SIRT1)-nuclear factor-κB (NF-κB) signaling pathway in reduction of brain injury by panax notoginseng saponins (PNS) in mechanically ventilated rats.Methods:Seventy-two SPF-grade male Sprague-Dawley rats, aged 10 weeks, weighing 357-377 g, were divided into 6 groups ( n=12 each) by a random number table method: sham operation group, model group, PNS low dose group, PNS medium dose group, PNS high dose group, and PNS high dose+ compound C group. PNS 12.5, 25 and 50 mg/kg were intraperitoneally injected in PNS low dose group, PNS medium dose group and PNS high dose group, respectively. In PNS high dose+ compound C group, PNS 50 mg/kg was intraperitoneally injected, and 10 min later compound C 0.2 mg/kg was injected via the tail vein. Normal saline 10 ml/kg was intraperitoneally injected in sham operation group and model group. Drugs or normal saline was injected at 30 min before mechanical ventilation in each group. Mechanical ventilation model: The animals were mechanically ventilated for 6 h, with ventilation frequency 40 times/min, tidal volume 40 ml/kg in model group; The animals were mechanically ventilated for 6 h, with tidal volume 10 ml/kg in sham operation group. Morris water maze test was used to detect the learning and memory function of rats, the concentrations of serum interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and dopamine (DA) were detected by enzyme-linked immunosorbent assay, the neuronal counts in the hippocampal CA1 region were determined by Nissl staining, and the expression of P2Y1 purine receptor (P2Y1R), dysbindin-1 and AMPK in hippocampal CA1 region was detected by Western blot. The phosphorylated SIRT1 (p-SIRT1) to SIRT1 ratio and phosphorylated NF-κB p65 (p-NF-κB p65) to NF-κB ratio in hippocampal CA1 region was calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in model group ( P<0.05). Compared with model group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the time of staying at the target platform quadrant was prolonged, the serum concentrations of IL-1β, IL-6 and TNF-α were decreased, the serum DA concentration was increased, the nerve count in hippocampal CA1 region was increased, the expression of P2Y1R and dysbindin-1 was down-regulated, the expression of AMPK was up-regulated, the p-SIRT1/SIRT1 ratio was increased, and the p-NF-κB p65/NF-κB p65 ratio was decreased in PNS low dose group, PNS medium dose group and PNS high dose group ( P<0.05). Compared with PNS high dose group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in PNS high dose+ compound C group ( P<0.05). Conclusions:The mechanism by which PNS reduces brain injury may be related to activation of the AMPK-SIRT1-NF-κB signaling pathway in mechanically ventilated rats.
