米诺环素对未成熟新生大鼠缺氧缺血性脑损伤的作用  

Role of minocycline in an immature rat model of hypoxic-ischemic brain damage

作　　者：邹晓萍[1] 李晓瑜[1] 李亮亮[1] 庄思齐[1] 车丽红[2] 

机构地区：[1]中山大学附属第一医院儿科,广州 510080 [2]中山大学附属第一医院病理科 ,广州 510080

出　　处：《中华儿科杂志》2010年第11期848-854,共7页Chinese Journal of Pediatrics

摘　　要：目的 研究米诺环素（minocycline,MN）对未成熟新生大鼠缺氧缺血性脑损伤（hypoxic-ischemic brain damage,HIBD）的作用.方法 生后2 d（P2）Sprague-Dawley（SD）大鼠192只,随机分成正常对照组、假手术组、HIBD组、HIBD＋MN组,每组48只.通过结扎左侧颈总动脉及8%氮氧混合气缺氧4 h,制作未成熟新生大鼠缺氧缺血性脑损伤模型.假手术组只分离左侧颈总动脉,正常组未予任何处理.HIBD＋MN组动物于HI后腹腔注射米诺环素45 mg/kg,此后2 d每24小时腹腔注射1次.HI后3 d,1、2、4周,行常规HE染色及病理评分,HI后3 d及2周,行抗O4、抗O1免疫组化及髓鞘脂碱性蛋白（MBP）免疫组化.HI后4周行神经行为学检测.结果 HIBD组病理可见脑室周围白质损伤,HIBD＋MN组病变较轻;O4阳性细胞计数：HIBD＋MN组与正常组差异无统计学意义,P＞0.05,而HIBD组较正常组,假手术组、HIBD＋MN组减少,差异有统计学意义（23.67±12.00 vs 52.89±10.68,39.28±11.78,41.63±8.41,P＜0.05）;O1阳性细胞计数：正常组,假手术组、HIBD组、HIBD＋MN组组间差异无统计学意义,P=0.093;MBP阳性纤维束计数：HIBD＋MN组与正常组、假手术组差别有统计学意义,P＜0.05,而HIBD组较正常组、假手术组、HIBD＋MN组减少,差异有统计学意义（14.71 ±7.42 vs 36.67±6.50,35.50±3.24,26.33±5.92,P＜0.05）;HIBD组HI后4周出现明显远期行为学异常,在斜坡试验、悬吊试验及Cylinder试验中,HIBD＋MN组与正常组、假手术组差别无统计学意义,P＞0.05;HIBD组与正常组、假手术组及HIBD＋MN组差异有统计学意义,P＜0.05;在旷场试验中,HIBD＋MN组与HIBD组差异无统计学意义,P=0.772,两组与正常组,假手术组差异均有统计学意义,P＜0.05.结论 米诺环素对未成熟新生大鼠缺氧缺血性脑损伤有早期及远期保护作用.Objective To establish a model of immature rat hypoxic-ischemic brain damage （HIBD） which was expected to be similar to periventricular leukomalacia in human preterm infants pathologically and neuroethologically, and to investigate the role of minocycline （MN） in this model.Method Totally 192 Sprague-Dawley rats （ postnatal day 2, P2）, of either sex, were randomly divided into 4 groups： normal-group, sham operation group, HIBD-group, HIBD ＋ MN group, each group had 48 rats. HIBD group and HIBD ＋ MN group survived the left common carotid artery （CCA） ligation followed by 4h exposure to 8% O2. Rats in sham operation group only survived the left CCA isolation. Rats in normal group were not treated with anything. In HIBD ＋ MN group, the rats were treated with intraperitoneal injection of minocycline 45 mg/kg, immediately after HI and every 24 h for 2 days. Brain tissues were collected on day 3, 1 week, 2 weeks, 4 weeks after HI, for hematoxylin-eosin staining and histological scoring. Frozen sections of the brains were stained with anti-O4, anti-O1 immunohistochemistry on day 3 after HI, and MBP immunohistochemistry 2 weeks after HI. Rats in the four groups underwent neuroethologic examination 4 weeks after HI. Result In the HIBD group, there were pathological changes in the periventricular white matter. The pathological changes were milder in HIBD ＋ MN group; There was no statistically significan defference between the normal group and HIBD ＋ MN group in the number of positively stained O4 cell （P 〉0.05 ）. The number of positively stained O4 cell in the HIBD group was significantly reduced, compared with that of normal group, sham operation group, and HIBD ＋ MN group （23.67 ± 12.00 vs. 52. 89 ± 10.68,39.28 ± 11.78,41.63 ± 8.41, P 〈 0.05 ）. The differences in the number of positively stained O1 cell among the normal group, sham operation group, HIBD group and HIBD ＋ MN group had no statistical significance（P = 0.093）. The numbers of myelin basic protein （MBP） po

关 键 词：缺氧缺血 脑 大鼠 米诺环素 白质软化病 脑室周围 

分 类 号：R686[医药卫生—骨科学]