Effect of methane on P2X 7R/NLRP3 signaling pathway during inflammatory responses in a rat model of spinal cord ischemia-reperfusion
10.3760/cma.j.issn.0254-1416.2020.02.025
- VernacularTitle:甲烷对脊髓缺血再灌注大鼠炎症反应时P2X 7R/NLRP3信号通路的影响
- Author:
Zhaokai ZENG
1
;
Haiyan XUE
;
Liping WANG
Author Information
1. 福建医科大学福总临床医学院 联勤保障部队第九〇〇医院 厦门大学附属东方医院 福建中医药大学福总教学医院 蚌埠医学院福总教学医院麻醉与围术期医学科，福州 350025
- From:
Chinese Journal of Anesthesiology
2020;40(2):225-228
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of methane on purinergic ion channel type 7 receptor (P2X 7R)/nod-like receptor protein 3 (NLRP3) signaling pathway during inflammatory responses in a rat model of spinal cord ischemia-reperfusion (I/R). Methods:Fifty-four clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 350-380 g, were divided into 3 groups ( n=18 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R) and methane group (group M). Rats underwent sham operation in group S. Spinal cord ischemia was induced by occlusion of the thoracic aorta combined with controlled hypotension for 9 min, followed by reperfusion in anesthetized animals in group I/R.Methane-rich saline 10 mg/kg was intraperitoneally administered immediately after onset of reperfusion in group M. Motor sensory deficit index (MSDI) in hind limbs was measured at 12, 24 and 48 h of reperfusion.The L 3-5 segment of spinal cord was removed at 48 h of reperfusion for determination of the number of normal neurons (by Nissl staining), the number of activated microglia and expression of P2X 7R, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), cysteine-requiring aspartate protease (caspase-1), interleukin-1beta (IL-1β) and IL-18 (by immunofluorescence staining) in anterior and posterior horns of spinal cord. Results:Compared with group S, the MSDI was significantly increased at 12, 24 and 48 h of reperfusion, and the number of normal neurons in anterior and posterior horns of spinal cord was decreased, the number of activated microglia was increased, and the expression of P2X 7R, NLRP3, ASC, caspase-1, IL-1β and IL-18 was up-regulated at 48 h of reperfusion in group I/R ( P<0.01). Compared with group I/R, the MSDI was significantly decreased at each time point of reperfusion, and the number of normal neurons in anterior and posterior horns of spinal cord was increased, the number of activated microglia was decreased, and the expression of P2X 7R, NLRP3, ASC, caspase-1, IL-1β and IL-18 was down-regulated at 48 h of reperfusion in group M ( P<0.05). Conclusion:The mechanism by which methane reduces inflammatory responses is related to inhibiting P2X7R/NLRP3 signaling pathway in a rat model of spinal cord I/R.
