Lipopolysaccharide preconditioning protects rats against cerebral ischemia reperfusion injury by reducing the damage of blood-brain barrier
10.3760/cma.j.issn.1673-4165.2022.11.006
- VernacularTitle:脂多糖预适应通过减轻血脑屏障破坏保护脑缺血再灌注大鼠
- Author:
Liqiang YANG
1
;
Weijie XU
;
Xin GUAN
Author Information
1. 昆明卫生职业学院，昆明 650600
- Keywords:
Brain ischemia;
Reperfusion injury;
Lipopolysaccharides;
Ischemic preconditioning;
Blood-brain barrier;
Inflammation;
Disease models, animal;
Rats
- From:
International Journal of Cerebrovascular Diseases
2022;30(11):826-831
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of lipopolysaccharide (LPS) preconditioning on cerebral ischemia reperfusion in rats.Methods:One hundred and twenty adult male SD rats were randomly divided into sham operation group, model group, low-dose LPS group (0.05 mg/kg), medium-dose LPS group (0.15 mg/kg), and high-dose LPS group (0.45 mg/kg). LPS was injected intraperitoneally for preconditioning, once a day for 7 consecutive days. Twenty-four hours after the last injection, the left middle cerebral artery occlusion model was induced by suture-occluded method. The model was reperfused 1.5 h after ischemia. At 24 h after reperfusion, the neurological deficit was evaluated by neurobehavioral score. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining. The serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. The expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase (MMP) -2 and MMP-9 in ischemic brain tissue was detected by Western blot analysis.Results:Compared with the sham operation group, blood-brain barrier permeability was increased in the model group, serum IL-1β, IL-6 and TNF-α were up-regulated, and the expression of TLR4, MMP-2 and MMP-9 proteins in ischemic brain tissue was up-regulated. Compared with the model group, the neurological impairment of each LPS intervention group was significantly reduced, the volume of cerebral infarction was significantly reduced, the permeability of blood-brain barrier was significantly reduced, the serum IL-1β, IL-6 and TNF-α were down-regulated, and the expression of TLR4, MMP-2 and MMP-9 protein in ischemic brain tissue was down-regulated, especially in the medium-dose group and the high-dose group.Conclusions:LPS preconditioning can induce the formation of ischemic tolerance, inhibit the activation of TLR4-MMP-2/MMP-9 signal pathway, reduce the damage and inflammation of blood-brain barrier structure, and thus play a neuroprotective role in rats with cerebral ischemia reperfusion.
