别嘌呤醇对未成熟大鼠脑白质损伤时自由基变化的影响

The effects of allopurinol on changes of free radicals in damaged white matter in premature rats

目的通过制作早产儿脑白质损伤动物模型,探讨自由基在早产儿脑白质损伤发病机制中的作用及别嘌呤醇的保护作用。方法利用新生1日龄SD大鼠32只行双侧颈总动脉结扎(BCAO)制作脑白质损伤模型,随机分为假手术组(Sham,n=8)、BCAO组(BCAO,n=12)及别嘌呤醇干预组(ALLO,n=12)。BCAO后48h检测脑白质XO、iNOS、Na+-K+-ATP酶、谷胱甘肽转移酶(GST)及.OH活力、尿酸(UA)及丙二醛(MDA)含量。结果MDA含量(nmol/mgprot):BCAO组(2.56±0.78)较Sham组(1.36±0.23)明显升高(P<0.01),而ALLO组(1.59±0.19)较BCAO组明显降低(P<0.01)。UA含量(mg/gprot):BCAO组(13.57±0.72)及ALLO组(12.34±0.21)均较Sham组(11.42±0.56)明显升高(P<0.01),而ALLO组较BCAO组明显降低(P<0.01);.OH活力(U/mgprot):与Sham组(156.0±8.07)比较,BCAO组(206.6±21.27)明显升高(P<0.01),而ALLO组(191.7±13.04)较BCAO组显著降低(P<0.05)。XO及iNOS活力:BCAO组较Sham组明显升高(P<0.01),而ALLO组较BCAO组明显降低(P<0.05);Na+-K+-ATP酶活力(μmolpi/mgprot/h):与Sham组(3.04±0.26)比较,BCAO组(2.30±0.37)及ALLO组(2.11±0.26)均明显降低(P<0.01),而ALLO组与BCAO组相比差异无显著性(P>0.05);GST活力(U/mgprot):与Sham组(56.75±4.22)比较,BCAO组(37.60±8.32)明显降低(P<0.01),而ALLO组(43.39±4.44)比BCAO组显著提高(P<0.05)。结论自由基在早产儿脑白质损伤中可能发挥了核心作用。别嘌呤醇对缺血引起的早产大鼠脑白质损伤具有一定的保护作用。

Objective The study was designed to investigate the role of free radicals in pathogenesis of white matter damage in premature infants and the protective effects of allopurinol Methods White matter damage animal model was established by bilateral carotid artery occulation （BCAO） . Thirtytwo Sprague Dawley （SD）newborn rats （aging 1 day old） were used and were divided randomly into three groups （Sham surgery, Sham; BCAO group, BCAO; allopurinol treated group, ALLO）. XO, iNOS, Na^＋ -K^＋ -ATPase and -OH activity, UA （uric acid） and MDA （malondial denyde） content changes in white mater was determined 48 h after BCAO, Results Compared with sham surgery group （ 1.36± 0. 23 ）, the MDA level （rmaol/mgprot） in BCAO group （2. 56 ± 0. 78） increased signifi- cantly （P〈0. 01） ; Compared with BCAO group, MDA level in ALLO group （1.59± 0. 19） decreased significantly （P〈0. 05）. The UA level （mg/gprot） in BCAO group （13.57 ± 0. 72） and that in ALLO group （12.34 ± 0. 21） were higher than that in sham group （11.42 ± 0. 56） （P〈0. 01 ） ; However, the UA level in ALLO group was lower than that in BCAO group （P〈0. 01）. Compared with sham sur- gery group （156. 0 ± 8. 07）, the .OH activity （U/mgprot）in BCAO group （206. 6± 21.27） increased significantly （P〈0. 01） ;Compared with BCAO group, -OH activity in ALLO group （191.7± 13.04） decreased significantly （P〈0. 05）. The XO and iNOS activity in BCAO group were higher than that in sham group （P〈0. 01） ; However, the XO and iNOS activity in ALLO group was lower than that in BCAO group （P〈0. 05）. Compared with sham surgery group （3.04± 0. 26 ）, the Na^＋ K^＋ - ATPase activity （μmolpi/mg prot per hour） in BCAO group （2. 30 ± 0. 37） and that in ALLO group （2. 11 ± 0. 26）decreased significantly （P〈0. 01 ）; However the difference between ALLO group and BCAO group was not statistically significant （P〈0. 05）. Compared with sham surgery group （56. 75 ± 4. 22）, the GST activity （U/mgprot） in BCAO group （37. 60 ±8. 32） decreased significantly （P〈0. 01）; However, the GST activity in ALLO group （43.39±4. 44） was higher than that in BCAO group （P〈0. 05）. Conclusions Free radicals may play a pivotal role in WMI） （white matter damage）. Allopurinol may have a potential protective effect on premature SD rat with ischemic WMD.