腺苷A1受体拮抗剂DPCPX对脑神经元低氧复氧损伤的影响

目的观察腺苷A1受体拮抗剂DPCPX对脑神经元低氧复氧(H/R)损伤的影响及其机制。方法通过建立体外培养大鼠大脑皮质神经元H/R损伤模型,观察终浓度分别为0(对照组)、25、50、100nmol/L的DPCPX对常氧(低氧0h)和低氧暴露8、12、24h后复氧24h的H/R神经元乳酸脱氢酶(LDH)释放量的影响,并检测了100nmol/LDPCPX对低氧暴露12h的H/R神经元丙二醛(MDA)含量及黄嘌呤氧化酶(XO)、Ca2 -ATP酶活性的影响。结果与对照组比较,100nmol/LDPCPX显著增加低氧暴露12h的H/R神经元LDH释放量(P<0·05),明显升高其MDA含量(P<0·01)和XO活性(P<0·05),明显降低其Ca2 -ATP酶活性(P<0·05)。结论DPCPX可加重培养神经元H/R损伤,其机制可能包括降低神经元抗氧化能力及Ca2 -ATP酶活性。

Effects of 1,3-dipropyl-8-cyclopentylxanthine, an adenosine A1 receptor antagonist, on brain neuronal damage induced by hypoxia and reoxygenation

Objective To observe the effects of 1,3-dipropyl-8-cyclopentylxanthine(DPCPX),an adenosine A1 receptor antagonist,on brain neurons damage induced by hypoxia and reoxygenation(H/R),and to elucidate the relevant mechanisms.Methods An in vitro cultured rat cerebral cortical neuronal H/R damage model was established;the effects of DPCPX were detected at final concentrations of 0(control),25,50,100nmol/L on the lactate dehydrogenase(LDH) release from normoxic neurons and H/R neurons which were treated with hypoxia for 8,12,24 hours followed by reoxygenation for 24 hours;the changes of malondialdehyde(MDA) content,activities of xanthine oxidase(XO) and Ca2 -ATPase in H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours brought by administration of DPCPX at the concentration of 100nmol/L were also determined by use of specific reagents.Results With addition of 100nmol/L DPCPX,the LDH release from H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours was significantly increased compared with that in control group(P<0.05).In addition,the content of MDA and the activity of XO were significantly increased(P<0.01,P<0.05) and the activity of Ca2 -ATPase was significantly decreased(P<0.05) in H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours with the addition of DPCPX at 100nmol/L compared with that in control group.Conclusion Administration of DPCPX at the concentration of 100nmol/L can aggravate neuronal damage in vitro induced by H/R,the mechanism may concern the decrease of both antioxidative capability and Ca2 -ATPase activity in H/R neurons.