基于Shh/Ptch1通路探讨艾司氯胺酮对脑缺血再灌注大鼠认知功能的影响OA

Objective To investigate the effect of Esketamine(EST)on cognitive function in rats with cerebral ischemia-reperfusion(CIR)by regulating the sonic hedgehog(Shh)/protein patched homolog 1(Ptch1)pathway.Methods A CIR rat model was estab-lished using the suture method,and was randomly assigned into CIR group,low EST group,high EST group,and high EST+Shh blocker(Cyclopamine)group,with 12 rats in each group.Then,12 normal rats were selected and only ligated without suture insertion as sham group.The rats in low EST group and high EST group were injected with 30 mg/kg and 60 mg/kg EST via the tail vein,respec-tively,and then intraperitoneally injected with the same volume of normal saline;the rats in high EST+Shh blocker group were in-jected with 60 mg/kg EST via the tail vein and then intraperitoneally injected with 10 mg/kg Shh blocker.The rats in sham group and CIR group were injected with the same volume of normal saline.The rats were treated once a day for 28 d.After the last administration,the neurological severity score(NSS)was used to evaluate the neurological damage.Morris water maze experiment was used to test the escape latency of the rats to evaluate the cognitive function.HE staining was used to observe the pathological changes in the hippocam-pal tissue.TUNEL staining was used to detect the apoptosis in the hippocampal tissue.ELISA was used to detect the levels of interleu-kin-6(IL-6)and CXC chemokine ligand 10(CXCL10)in the hippocampal tissue.Western blot was used to detect the expressions of Shh and Ptch1 proteins in the hippocampal tissues.Results Compared with CIR group,the escape latency,NSS score,the apopto-sis rate,IL-6,and CXCL10 levels decreased in low EST group and high EST group,while the Shh and Ptch1 protein levels increased(P＜0.05).Moreover,the improvemen of the above indicators was better in high EST group than in low SET group(P＜0.05).Compared with high EST group(P＜0.05),the escape latency,NSS score,the apoptosis rate,IL-6,and CXCL10 levels increased in high EST+Shh blocker group(P＜0.05),while the Shh and Ptch1 protein levels decreased(P＜0.05).Conclusion EST may alleviate the neuro-inflammation and improve the cognitive function in CIR rats by activating Shh/Ptch1 signaling pathway.