Research Of Exercise Preconditioning Exerts Anti-Inflammatory Effects In Cerebral Ischemia/Reperfusion Injury Via TLR4/NF-κB Signaling Pathway

Objective:To investigate the anti-inflammatory mechanism of exercise preconditioning on cerebral ischemia reperfusion injury via TLR4/NF-κB signaling pathway.Methods:36 male SD rats were randomly divided into sham group, model group, exercise preconditioning group (n=12). A transient middle cerebral artery occlusion (MCAO) cerebral ischemia/reperfusion(I/R) model was prepared by using the modified Longa’s intraluminal filament technique. After I/R 2h、24h, all rats in each group were assessed for neurological deficit score. After I/R 24h, the pathological changes in ischemic cortex was observed by using HE staining method; the infarct volume was measured by using TTC staining method; the expression of TLR4、NF-κB was observed by using IHC method; the content of serum TNF-α、IL-1β was detected by using ELISA.Results:1. Neurological deficit scores:The sham group rats had no significant neurological deficit at each time point. After I/R 2h、24h, compared with sham group, the neurological deficit scores of rats in model group and exercise preconditioning group were both increased significantly (P< 0.01).After I/R 24h, Compared with model group, exercise preconditioning reduced the neurological deficit scores of rats significantly (P<0.01)2. Histopathology observation:After I/R 24h, the rats in sham group have no pathological changes, the morphological structure of brain tissue was distinct, nerve cells were normal. Compared with sham group, the ischemia cortex area in model group showed patchy distribution of loose structure, interstitial edema, significant vacuolar changes, deeply stained nuclear pyknosis, nerve cells arranged in disorder, and ischemia area surrounding inflammatory infiltration is obvious. Compared with model group, exercise preconditioning alleviated the degree of damage of brain tissue, brain edema, inflammatory cells infiltration, increased the number of neurons and reduced necrosis of neurons.3. The volume of cerebral infarction:After I/R 24h, the rats in sham group had no cerebral infarction, the model group had obvious infracts (P<-0.01). Compared with model group, exercise preconditioning significantly reduced the volume of cerebral infarction (P< 0.01)4. The expression of TLR4、NF-κB in ischemic penumbra:Afrer I/R 24h, compared with sham group, the number of positive cells and the integral optical density values of TLR4 and NF-κB were both significantly increased (P<0.01). Compared with model group, exercise preconditioning significantly reduced the number of positive cells and the integral optical density values of TLR4 and NF-κB (P<0.01).5. The content of serum TNF-α、IL-1β:After I/R 24h, compared with sham group, the content of TNF-α、IL-1β in serum of model group increased significantly (P<0.01); compared with model group, exercise preconditioning significantly decreased the content of serum TNF-α、IL-1β(P <0.01).Conclusions:1. Exercise preconditioning can reduce neurological deficit scores, improving neural function defect symptoms of rats after cerebral I/R.2. Exercise preconditioning can reduce the degree of pathological damage in ischemic cortex and the volume of cerebral infarction of rats after cerebral I/R, exerting a neuroprotective effect.3. The neuroprotective mechanism of exercise preconditioning may be related to it can down regulate the expression of TLR4 and NF-kB in ischemic penumbra, reduce peripheral serum TNF-α、IL-1β levels of rats after cerebral I/R, thereby inhibiting the inflammatory cascade reaction.