AMPA受体拮抗剂对新生鼠缺氧缺血性脑损伤自由基的影响

Effect of AMPA receptor antagonist on free radicals in newborn rats with hypoxic-ischemic brain damage

目的:探讨α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid,AMPA)受体拮抗剂GYKI-52466对缺氧缺血新生鼠脑组织自由基的影响。方法:选用7日龄Wistar大鼠30只,随机分为3组,假手术组,缺氧缺血组和治疗组。治疗组在缺氧缺血后即刻开始予GYKI-5246610mg/kg腹腔注射,每小时注射1次,共4次。缺氧缺血组予等量生理盐水腹腔注射。于处置后24h检测脑组织中超氧化物歧化酶(superoxidedismutaseSOD)、谷胱甘肽、丙二醛水平。结果:缺氧缺血组脑组织SOD,GSH水平分别为(1.47±0.15)mkat、(75.03±5.22)mg/g,明显低于假手术组(2.51±0.16)mkat、(88.66±4.50)mg/g(t=3.237～15.573,P均<0.001);MDA含量为(8.03±0.64)pmol/g,较假手术组(5.12±0.57)pmol/g显著升高(t=6.253～15.373,P<0.001)。而治疗组脑组织SOD、谷胱甘肽水平分别为(2.73±0.21)mkat、(83.47±6.38)mg/g,明显高于缺氧缺血组(P<0.001;P<0.005);丙二醛含量为(6.07±0.68)pmol/g,较缺氧缺血组显著下降(P<0.001)。结论:AMPA拮抗剂可通过拮抗氧自由基发挥对缺氧缺血性脑损伤时脑的保护作用。

AIM:To determine the effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazo lepropionic acid(AMPA) receptor antagonist on free radicals in newborn rats with hypoxic-ischemic brain damage(HIBD). METHODS:Thirty 7-day-old Wistar rats were randomly divided into sham-operat ed group,hypoxic-ischemic group and GYKI-52466 treatment group.The rats in the treatment group were intraperitoneally injected with 10 mg/kg GYKI-52466 immed iately after hypoxia ischemia,once an hour, totally 4 times.The rats in the hypo xic-ischemic group were given intraperitoneal injection of normal saline at the same dosage.Superoxide dismutase(SOD)activity,reduced glutathione(GSH)and m alondialdehyde(MDA)levels were measured 24 hours after treatment. RESULTS:The SOD activity and GSH level in the hypoxic-ischemic group were(1.4 7±0.15)mkat and(75.03±5.22)mg/g,significantly lower than those in the sham-op erated group[(2.51±0.16)mkat and(88.66±4.50)mg/g](t=3.237-15.573,P< 0.001). The MDA level was(8.03±0.64) pmol/g,significantly higher than that in the sham -operated group[(5.12±0.57)pmol/g](t=6.253-15.373,P< 0.001).Compared with the hypoxic-ischemic group, the SOD activity and GSH level were significantly high er[(2.73±0.21)mkat and(83.47±6.38) mg/g](P< 0.001,P< 0.005),and the MDA conten t was significantly lower in the treatment group[(6.07±0.68) pmol/g](P<0.001). CONCLUSION:AMPA receptor antagonist can prevent brain against HIBD by inhibiti ng the release of free radicals.