腺苷A_1受体拮抗剂DPCPX对脑神经元低氧复氧损伤的影响  

Effects of 1,3-dipropyl-8-cyclopentylxanthine,an adenosine A_1 receptor antagonist,on brain neuronal damage induced by hypoxia and reoxygenation

作　　者：王静雯[1] 汪海[1] 

机构地区：[1]军事医学科学院卫生学环境医学研究所,天津300050

出　　处：《解放军医学杂志》2008年第7期803-805,共3页Medical Journal of Chinese People's Liberation Army

摘　　要：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。Objective To observe the effects of 1,3 dipropyi-8-cyciopentyixanthine （DPCPX）, an adenosine A1 receptor antagonist, on brain neurons damage induced by hypoxia and rcoxygenation （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 rcoxygenation 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 rcoxygenation 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 100nmoi/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.

关 键 词：神经元 缺氧/复氧损伤 受体 腺苷A1 活性氧 Ca2+转运ATP酶 

分 类 号：R338.1[医药卫生—人体生理学]