Zhimu saponin B-Ⅱ reduces cerebral ischemia-reperfusion induced injury in rats by activating the cAMP/PKA/CREB pathway
Objective To observe the therapeutic effect of Zhimu saponinB-11(TB-Ⅱ)on cerebral ischemia-reperfusion injury(CIRI)by inhibiting the cAMP/PKA/CREB pathway.Methods Rats were randomly divided into 6 groups:sham surgery group,model group,low-dose TB-Ⅱ group(10 mg/kg),medium dose TB-Ⅱ group(20 mg/kg),high-dose TB-Ⅱ group(40 mg/kg),and nimodipine treatment group(12 mg/kg).After establishing a rat model of middle cerebral artery occlusion using the Longa suture method,the neurological function scores,infarct area,brain water content,and Evans blue(EB)content of each group of rats were measured;observe the structural damage and neuronal apoptosis of brain neurons through Nissl staining and immunofluorescence staining;the expression levels of inflammatory factors and related pathway proteins were detected by ELISA and Western Blot.Results Compared with sham surgery group,the EB content in model group increased(P<0.05);compared with model group,the brain water content,EB content,and cerebral infarction area of nimodipine group decreased(P<0.05,P<0.01),while the brain water content of the medium and high dose groups decreased(P<0.05);the EB content and cerebral infarction area of each dose group decreased(P<0.05,P<0.0 1);meanwhile,all dose groups of TB-Ⅱ were able to downregulate interluekin-1(IL-1)to varying degrees IL-1β,IL-6 and tumor necrosis factor-α(TNF-α);the secretion of inflammatory factors was regulated(P<0.05),and the expression of AQP-4 protein was reduced through the PKA/CREB pathway(P<0.05).Conclusion This study revealed that TB-Ⅱ alleviates cerebral ischemia-reperfusion injury in rats through the PKA/CREB pathway.