Abstract

Objective To investigate the effects of oxymatrine (OMT) on sphingosine kinase 2 (SphK2) and Claudin-5 (claudin-5) in rats withacute cerebral infarction (ACI) . Methods Rat models of acute middle cerebral artery occlusion (MCAO) were established. They were randomly divided into model group and OMT treatment group (low, medium and high dose groups) , with 10 rats in each group. Another 10 normal rats were enrolled as control group. The low, medium and high dose OMT groups were intraperitoneally injected with 30, 60 and 120 mg/kg OMT, respectively. The model group and the control group were injected with the same volume of normal saline, once per 12h, for a total of 4 times. The rats were sacrificed at 12h after the last injection, and brain tissueswere harvested. The size of infarction in each group was determined by TTC staining. The water content of brain tissues was determined by dry and wet method. The contents of serum interleukin-1β (IL-1β) , interleukin-6 (IL-6) and interleukin-10 (IL-10) in each group were detected by ELISA. The expression levels of SphK2 mRNA and claudin-5 mRNA in each group were detected by RT-PCR. The relative expression quantities of SphK2 and claudin-5 protein were measured by Western blot. Results Compared with model group, percentage size of infarctionand water content in brain tissuesof OMT treatment group were significantly decreased (all P<0.05) , showinga dose-dependencemanner. Compared with control group, the model grouphad increased contents of IL-1β, IL-6 and IL-10, higher relative expression quantities of SphK2 mRNA and SphK2 protein, and lowerrelative expression quantities of claudin-5 mRNA and claudin-5 protein (all P<0.05) . Compared with model group, the OMT treatment groups had lower contents of IL-1β, IL-6 and IL-10, decreased relative expression quantities of SphK2 mRNA and SphK2 protein, and higher relative expression quantities of claudin-5 mRNA and claudin-5 protein (all P<0.05) , showing adose-dependence manner. Conclusion OMT may significantly reduce cerebral infarction sizeand water content of brain tissues in ACI rats, and inhibit inflammatory response. The mechanism of theseactionsmay be related to the down-regulation of SphK2 and up-regulation of claudin-5 by OMT. Key words: Oxymatrine; Acute cerebral infarction; Rat; Sphingosine kinase 2; Claudin 5

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