Abstract
BackgroundExcitatory amino acid toxicity, oxidative stress, intracellular calcium overload, as well as inflammation and apoptosis are involved in the pathological process after cerebral ischemic reperfusion injury. Picrodide 2 could inhibit neuronal apoptosis and play anti-oxidant and anti-inflammation role in cerebral ischemia/reperfusion injuries, but the exact mechanism is not very clear. This study aims to explore the anti-inflammation mechanism of picroside 2 in cerebral ischemic reperfusion injury in rats.MethodsThe middle cerebral artery occlusion reperfusion models were established with intraluminal thread methods in 90 adult healthy female Wistar rats. Picroside 2 and salvianic acid A sodium were respectively injected from tail vein at the dosage of 10 mg/kg for treatment. The neurobehavioral function was evaluated with Bederson's test and the cerebral infarction volume was observed with tetrazolium chloride (TTC) staining. The apoptotic cells were counted by in situ terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The immunohistochemistry stain was used to determine the expressions of toll-like receptor 4 (TLR4), nuclear transcription factor κB (NFκB) and tumor necrosis factor α (TNFα). The concentrations of TLR4, NFκB and TNFα in brain tissue were determined by enzyme linked immunosorbent assay (ELISA).ResultsAfter cerebral ischemic reperfusion, the rats showed neurobehavioral function deficit and cerebral infarction in the ischemic hemisphere. The number of apoptotic cells, the expressions and the concentrations in brain tissue of TLR4, NFκB and TNFα in ischemia control group increased significantly than those in the sham operative group (P < 0.01). Compared with the ischemia control group, the neurobehavioral scores, the infarction volumes, the apoptotic cells, the expressions and concentrations in brain tissue of TLR4, NFκB and TNFα were obviously decreased both in the picroside 2 and salvianic acid A sodium groups (P < 0.01). There was no statistical difference between the two treatment groups in above indexes (P > 0.05).ConclusionsPicroside 2 could down-regulate the expressions of TLR4, NFκB and TNFα to inhibit apoptosis and inflammation induced by cerebral ischemic reperfusion injury and improve the neurobehavioral function of rats.
Highlights
Excitatory amino acid toxicity, oxidative stress, intracellular calcium overload, as well as inflammation and apoptosis are involved in the pathological process after cerebral ischemic reperfusion injury
Our previous experiments[16,17,18,19] indicated that picroside 2 could inhibit the expressions of inducible nitric oxide synthase, nuclear transcription factor κB (NFκB) and inhibitor of NFκB (IκB), and reduce the expressions of Caspase-3 and poly ADP-ribose polymerase (PARP) to inhibit the neuronal apoptosis and improve the neurobehavioral function of rats with cerebral ischemia reperfusion injury
Fifteen rats were randomly selected as a sham operated group (SO), and the rest 75 rats were subjected to the experimental middle cerebral artery occlusion 2 h and reperfusion 22 h (MCAO/R) models with intraluminal monofilament suture from left external-internal carotid artery [20,21]
Summary
Excitatory amino acid toxicity, oxidative stress, intracellular calcium overload, as well as inflammation and apoptosis are involved in the pathological process after cerebral ischemic reperfusion injury. Picrodide 2 could inhibit neuronal apoptosis and play anti-oxidant and anti-inflammation role in cerebral ischemia/reperfusion injuries, but the exact mechanism is not very clear. Our previous experiments[16,17,18,19] indicated that picroside 2 could inhibit the expressions of inducible nitric oxide synthase (iNOS), nuclear transcription factor κB (NFκB) and inhibitor of NFκB (IκB), and reduce the expressions of Caspase-3 and poly ADP-ribose polymerase (PARP) to inhibit the neuronal apoptosis and improve the neurobehavioral function of rats with cerebral ischemia reperfusion injury. We established the experimental MCAO/R model to investigate the effects of picroside 2 via tail vein injection on TLR4-NFκB signal transduction pathway and cell apoptosis, and to explore its antiinflammatory mechanism in cerebral ischemic reperfusion injury
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