Effect of arctigenin on cognitive dysfunction induced by sevoflurane anesthesia in aged rats and the role of autophagy-mediated pyroptosis
10.3760/cma.j.cn131073-20240510-00208
- VernacularTitle:牛蒡子苷元对七氟烷麻醉致老龄大鼠认知功能障碍的影响及自噬介导的细胞焦亡在其中的作用
- Author:
Pengcheng WANG
1
;
Zhen WANG
;
Guoqing ZHANG
;
Yanwen DAI
;
Tiezhu HOU
;
Zhisong LI
Author Information
1. 驻马店市中心医院麻醉科，驻马店 463000
- Publication Type:Journal Article
- Keywords:
Arctigenin;
Sevoflurane;
Cognition dysfunction;
Aged;
Autophagy;
Pyroptosis
- From:
Chinese Journal of Anesthesiology
2025;45(2):163-169
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of arctigenin (ARG) on cognitive dysfunction induced by sevoflurane anesthesia in aged rats and the role of autophagy-mediated pyroptosis.Methods:Fifty SPF male Sprague-Dawley rats, aged 18-20 months, weighing 550-600 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (C group), sevoflurane anesthesia group (Sev group), sevoflurane anesthesia+ ARG group (Sev+ ARG group), sevoflurane anesthesia+ autophagy inducer rapamycin group (Sev+ RAPA group), and sevoflurane anesthesia+ ARG+ autophagy inhibitor 3-methyladenine (3-MA) group (Sev+ ARG+ 3-MA group). Except for group C, the rats in the other groups inhaled 6% sevoflurane for 3 h to establish the cognitive impairment model. At 30 min before anesthesia, ARG 20 mg/kg was intraperitoneally injected in Sev+ ARG group, rapamycin 7.5 mg/kg was intraperitoneally injected in Sev+ RAPA group, and ARG 20 mg/kg (dissolved in dimethyl sulfoxide) was intraperitoneally injected, followed by immediate intraperitoneal injection of 3-MA 1.5 mg/kg in Sev+ ARG+ 3-MA group. The equal volume of dimethyl sulfoxide was intraperitoneally injected in C group and Sev group. The Morris water maze test was conducted to assess the cognitive function at 48 h after the end of administration. After completion of the Morris water maze test, the hippocampal tissue was taken under deep anesthesia for observation of the pathological changes (after HE staining) which were scored and for determination of neuronal pyroptosis (after propidium iodide staining) and expression of neuronal autophagy-related proteins (microtubule-associated protein 1 light chain 3 [LC3], Beclin-1, p62), pyroptosis-related proteins (NOD-like receptor protein 3 [NLRP3], apoptosis-associated speck-like protein containing a CARD [ASC], pro-cysteine aspartate-specific protease 1 [pro-caspase-1], cleaved-caspase-1, gasdermin D [GSDMD], and N-terminal fragment of gasdermin D [GSDMD-N], interleukin-1β [IL-1β] and IL-18). Results:Compared with C group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the hippocampal injury score and neuronal pyroptosis rate were increased, LC3Ⅱ/LC3Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, the expression of p62, NLRP3, ASC, IL-1β and IL-18 was up-regulated, and the cleaved-caspase-1/pro-caspase-1 ratio and GSDMD-N/GSDMD ratio were increased in Sev group ( P<0.05). Compared with Sev group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the hippocampal injury score and neuronal pyroptosis rate were decreased, LC3Ⅱ/LC3Ⅰ ratio was increased, the expression of Beclin-1 was up-regulated, the expression of p62, NLRP3, ASC, IL-1β and IL-18 was down-regulated, and the cleaved-caspase-1/pro-caspase-1 ratio and GSDMD-N/GSDMD ratio were decreased in Sev+ ARG group and Sev+ RAPA group ( P<0.05). Compared with Sev+ ARG group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the hippocampal injury score and neuronal pyroptosis rate were increased, LC3Ⅱ/LC3Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, the expression of p62, NLRP3, ASC, IL-1β and IL-18 was up-regulated, and the cleaved-caspase-1/pro-caspase-1 ratio and GSDMD-N/GSDMD ratio were increased in Sev+ ARG+ 3-MA group ( P<0.05). Conclusions:AGR can alleviate sevoflurane anesthesia-induced cognitive dysfunction in aged rats, and the mechanism is related to reduction of autophagy-mediated cell pyroptosis.
