Effect of intermittent fasting on postoperative cognitive function in aged rats and role of JAK2/STAT3 signaling pathway
10.3760/cma.j.cn131073.20231221.00506
- VernacularTitle:间歇性禁食对老龄大鼠术后认知功能的影响及JAK2/STAT3信号通路在其中的作用
- Author:
Lei WANG
1
;
Chenyi YANG
;
Xiaoqing WANG
;
Zhiqiang NIU
;
Haiyun WANG
Author Information
1. 天津医科大学三中心临床学院，天津 300170
- Keywords:
Fasting;
Aged;
Postoperative cognitive complications;
Janus kinase 2;
STAT3 transcription factor
- From:
Chinese Journal of Anesthesiology
2024;44(5):558-563
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of intermittent fasting on postoperative cognitive function in aged rats and the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in it.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), postoperative cognitive dysfuction (POCD) group (group P), intermittent fasting + POCD group (group IF+ P), and intermittent fasting+ JAK2/STAT3 signaling pathway agonist C-A1+ POCD group (group IF+ A+ P). IF+ P group and IF+ A+ P group underwent a 4-week intermittent fasting procedure: fasting for 24 h followed by free eating for 24 h, without limiting water intake throughout the entire process, in addition C-A1 100 μg/kg was intraperitoneally injected daily during intermittent fasting in IF+ A+ P group. Rats underwent exploratory laparotomy under sevoflurane anesthesia to prepare POCD models in P group, IF+ P group and IF+ A+ P group. Three days after surgery, open field tests were conducted to evaluate the autonomous motor function of rats, and Morris water maze tests were conducted to evaluate the cognitive function of rats on 3-7 days after surgery. After the Morris water maze tests, the rats were sacrificed and the hippocampal CA1 area was removed for determination of the expression of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3) (by Western blot) and contents of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for microscopic examination of pathological changes of hippocampal CA1 region (using HE staining). Results:There was no statistically significant difference in the speed, distance and duration of stay at the center of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage occurred in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were decreased ( P<0.05), and the pathological damage in the hippocampal CA1 area was significantly alleviated in IF+ P group. Compared with IF+ P group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage in the hippocampal CA1 area was aggravated in group IF+ A+ P. Conclusions:Intermittent fasting can improve postoperative cognitive function in aged rats, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway and reducing the neuroinflammatory responses in the hippocampal CA1 region.
