Effect of DA-JC4 on postoperative neuroinflammatory responses in aged rats
10.3760/cma.j.cn131073.20191206.00518
- VernacularTitle:DA-JC4对老龄大鼠术后神经炎症反应的影响
- Author:
Hongyan GONG
1
;
Fang ZHENG
;
Zhichao ZUO
;
Jingjing LIU
;
Qingzhi WANG
;
Guoan ZHAO
Author Information
1. 新乡医学院第一附属医院麻醉科 453000
- From:
Chinese Journal of Anesthesiology
2020;40(5):588-591
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist DA-JC4 on postoperative neuroinflammatory responses in aged rats.Methods:Forty-five Sprague-Dawley rats, aged 21-23 months, weighing 530-630 g, provided by the Animal Experiment Center of Medical School of Zhengzhou University, were assigned into 3 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O) and DA-JC4 group (group G). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O and G groups.In group G, DA-JC4 10 nmol/kg (dissolved in 1 ml of sterile normal saline) was intraperitoneally injected immediately after the end of operation and at 24 and 48 h after operation.Western blot was used to determine the expression of hippocampal Bax, Bcl-2, activated caspase-3, Beclin-1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), high-mobility group box 1 protein (HMGB1), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) on day 3 after surgery.The Morris water maze test was performed on days 14-18 after operation to assess the cognitive function. Results:Compared with group S, the escape latency was significantly prolonged on days 15-18 after operation in group O and on day 18 after operation in group G, and the number of crossing the original platform was reduced, the time spent in the target quadrant was shortened, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was up-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was down-regulated in O and G groups ( P<0.05). Compared with group O, the escape latency was significantly shortened, and the number of crossing the original platform was increased, the time spent in the target quadrant was prolonged, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was down-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was up-regulated in group G ( P<0.05). Conclusion:The mechanism by which DA-JC4 reduces postoperative cognitive dysfunction may be related to inhibiting neuroinflammatory responses in aged rats.