Effects of picroside Ⅱ on blood-brain barrier injury in neonatal rats with hypoxic ischemic brain damage by modulating the cAMP/PKA signaling pathway
Objective To investigate the effects of picroside Ⅱ(P-Ⅱ)on blood-brain barrier(BBB)injury in neonatal rats with hypoxic-ischemic brain injury(HIBD)by modulating cAMP/PKA signaling pathway.Methods HIBD model was established.Neonatal rats were divided into sham surgery group(Sham group),model group(HIBD group),low dose picroside Ⅱ group(P-Ⅱ-L),medium dose picroside Ⅱ group(P-Ⅱ-M),high dose picroside Ⅱ group(P-Ⅱ-H),high dose picroside Ⅱ+PKA inhibitor group(P-Ⅱ-H+H89)according to random number table method.Brain water content of 25 subjects in each group was detected.The content of MDA,ROS,NADPH activity and cAMP concentration were detected by ELLISA method.HE staining was used to observe brain morphology.The BBB permeability was detected by EB staining.DyLight 488 fluo-rescent marker was used to detect IgG leakage.Western blot was ap-plied to detect the expression levels of Claudin-5,Occludin,VE-Cad-herin,β-Catenin,and p-PKA,PKA,p-CREB,and CREB proteins.Results Brain water content,MDA,ROS content,NADPH activity and IgG expression were increased in HIBD group.The concentration of Claudin-5,Occludin,VE-Cadherin,β-Catenin,cAMP and the expression levels of P-PKA/PKA and P-CREB/CREB were decreased (P<0.05);Compared with HIBD group,brain water content,MDA,ROS content,NADPH activity and IgG of neonatal rats in P-Ⅱ-L,P-Ⅱ-M and P-Ⅱ-H groups were decreased in a dose-dependent manner.The concentrations of Claudin-5,Occludin,VE-Cadherin,β-Catenin,cAMP and the expression levels of P-PKA/PKA and P-CREB/CREB were increased in a dose-dependent manner(P<0.05).Compared with P-Ⅱ-H group,brain water content,MDA,ROS content,NADPH activity and IgG expression were increased in P-Ⅱ-H+H89 group.The concentration of Claudin-5,Occludin,VE-Cadherin,β-Catenin,cAMP and the expression levels of P-PKA/PKA and P-CREB/CREB were decreased(P<0.05).Conclusion P-Ⅱ protects HIBD neonatal rats from BBB injury by activating the cAMP/PKA signaling pathway.
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