Effect of neferine on blood-brain barrier in rats with ischemic stroke by regulating CCL2-CCR2 signal pathway
Objective:To investigate the impact of neferine(NEF)on the blood-brain barrier in ischemic stroke(IS)rats by regulating the CC chemokine ligand 2(CCL2)-CC chemokine receptor 2(CCR2)signal pathway.Methods:SD rats were randomly divided into model group,low-dose NEF group(NEF-L group,25 mg/kg NEF),high-dose NEF group(NEF-H group,50 mg/kg NEF),and high-dose NEF+CCR2 antagonist group(NEF-H+RS102895 group,50 mg/kg NEF+10 mg/kg RS102895),sham opera-tion group(Sham group),with 15 rats in each group.The neurological function scores of rats in each group were compared.The perme-ability of blood-brain barrier of rats in each group was evaluated by Evans blue(EB)permeation method.The water content of brain tis-sue of rats in each group was determined by dry and wet weight method.The expression levels of CCL2 and CCR2 mRNA in rat brain tissue were measured by real-time fluorescence quantitative PCR(RT-qPCR).The expression levels of CCL2,CCR2,ZO-1 and Clau-din-5 proteins in rat brain tissue were detected by Western blot.Results:Compared with Sham group,the neural function score,EB content,water content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of the model group were obvi-ously higher(P<0.05),the expression levels of ZO-1 and Claudin-5 were lower(P<0.05).Compared with the model group,the neuro-logical function score,water content,EB content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of rats in the NEF-H group were obviously lower(P<0.05),the expression levels of ZO-1 and Claudin-5 were obviously higher(P<0.05).RS102895 enhanced the protective effect of NEF on the blood-brain barrier in IS rats.Conclusion:NEF may protect the blood-brain barrier of IS rats by inhibiting CCL2-CCR2 signal pathway.
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