Inhibition of the neutral sphingomyelinase-2 pathway protects against cerebral ischemia reperfusion injury in rats
10.3760/cma.j.issn.1673-4165.2018.06.009
- VernacularTitle:抑制中性鞘磷脂酶-2通路保护脑缺血再灌注大鼠
- Author:
Gang LI
1
;
Xinlei GUAN
;
Xifeng WANG
;
Min YU
;
Wen XIONG
;
Lan WANG
;
Wei SHEN
Author Information
1. 华中科技大学同济医学院附属普爱医院神经内科
- Keywords:
Brain Ischemia;
Reperfusion Injury;
Sphingomyelin Phosphodiesterase;
Receptor,Adenosine A2B;
p38 Mitogen-Activated Protein Kinases;
Neuroprotective Agents;
Disease Models,Animal;
Rats
- From:
International Journal of Cerebrovascular Diseases
2018;26(6):444-449
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of neutral sphingomyelinase-2 (nSMase2) pathway on cerebral edema and cerebral injury in cerebral ischemia-reperfusion injury in rats. Methods Seventy-six adult male SD rats were randomly divided into sham operation group (n = 12), modeling group (n = 16), vehicle group (n = 16), SB203580 (a p38 mitogen activated protein kinase [MAPK] inhibitor) treatment group (n = 16) , and MRS1754 (a selective adenosine A2B receptor [A2B AR] antagonist) treatment group (n = 16) according to the random number table. A suture-occluded method was used to induce a middle cerebral artery ischemia-reperfusion model. Vehicle, SB203580, and MRS1754 were injected into the lateral ventricles 30 min before model preparation, the neurological function score was performed after ischemia-reperfusion for 24 h. 2,3,5 triphenyltetrazolium staining was used to detect the infarct volume. The water content of brain tissue was detected by dry-wet weight method. Western blot analysis was used to detect the expression of nSMase 2 and p38 MAPK in ischemic brain tissue. Immunohistochemical staining was used to detect the expression of nSMase 2 in ischemic brain tissue. Results MRS1754 significantly decreased neurobehavioral score (P < 0. 05) and reduced cerebral infarction volume (P < 0. 05) in rats. Both MRS1754 and SB203580 significantly decreased the water content of ischemic brain tissue (all P < 0. 05). In addition, MRS1754 also significantly decrease the phosphorylation of p38 MAPK after ischemia-reperfusion and decreased the expression level of nSMase 2 (P < 0. 01). Conclusion Regulation of A2BAR and p38 MAPK of nSMase upstream may play a neuroprotective role after cerebral ischemia-reperfusion injury.
