1,7-二甲基黄嘌呤对氧糖剥夺再灌注神经元细胞和缺血再灌注损伤小鼠脑组织的保护作用及其机制OA

Objective To investigate the protective effects of 1,7-dimethylxanthine(paraxanthine)on oxygen-glucose deprivation/reperfusion(OGD/R)-treated neuronal cells and on the brain tissue of model mice with ischemia/reperfusion(I/R)in-jury,as well as the underlying mechanism.Methods Primary cortical neurons were divided into a control group,an OGD/R group,and an OGD/R+paraxanthine group,which were treated with normal neuronal culture medium,OGD/R,and OGD/R plus paraxanthine,respectively.The viability of neurons in the three groups was measured by CCK-8 assay.The expression level of phosphorylated protein kinase B(p-Akt)in the neurons from the three groups was detected by Western blot.C57BL/6 mice were randomly divided into a Sham group,an I/R group,and an I/R+paraxanthine group.Mice in the Sham group underwent sham operation(external carotid arteriotomy only),those in the I/R group were subjected to I/R model establishment(middle cerebral artery occlusion for 1.5 h followed by reperfusion),and those in the I/R+paraxanthine group received I/R model establishment plus paraxanthine treatment(intraperitoneal injection of paraxanthine immediately after reperfusion).At 24 h after reperfusion,the modified neurological severity score(mNSS)was used to assess the degree of neurological impairment in each group.TTC stai-ning was used to observe the cerebral infarct volume in each group,and the percentage of infarct volume relative to the total brain volume was calculated.Results The neuronal viability in the OGD/R+paraxanthine group was significantly higher than that in the OGD/R group(F=115.30,t=3.86,P＜0.05).Compared with the control group,the relative expression levels of p-Akt in the OGD/R group and the OGD/R+paraxanthine group were significantly increased(F=15.07,t=9.81,4.55,P＜0.05).Compared with the I/R group,the mNSS of mice in the I/R+paraxanthine group was significantly decreased(F=49.05,t=2.33,P＜0.05),and the cerebral infarct volume was significantly reduced(F=675.30,t=9.12,P＜0.05).Conclusion Paraxanthine has a cer-tain protective effect against OGD/R-induced neuronal injury and I/R-induced cerebral infarction in mice.The underlying mecha-nism may be related to the upregulation of p-Akt levels in neurons.