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新生期缺氧缺血性脑白质损伤大鼠模型比较研究

Comparative study of neonatal rat models of hypoxia-ischemia induced white matter injury of brain

摘要目的 探讨3种不同方式建立的新生期缺氧缺血性脑白质损伤大鼠模型的异同,为深入研究早产儿脑白质损伤选择理想的动物模型提供理论基础.方法 对3日龄Wistar大鼠采用3种不同的缺氧缺血方法建立脑白质损伤模型,分别为:左侧颈总动脉结扎伴低氧(6%O2) 30 min、左侧颈总动脉结扎伴低氧(6%O2)4 h和双侧颈总动脉结扎伴低氧(8%O2)30min.比较各组大鼠脑病理形态学变化、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和髓鞘碱性蛋白(myelin basic protein,MBP)免疫组织化学染色以及眼部变化.结果 左侧颈总动脉结扎伴低氧(6%O2)30min侧脑室周围白质组织结构稀疏模糊但无坏死灶;左侧脑室周围白质区GFAP免疫染色强度[(5 021.63 ±358.92) OD]增加程度最低(P <0.000 1),MBP免疫染色强度[(18488.63 ±1 822.62) OD]降低程度最低(P<0.000 1);左侧睁眼时间延迟.左侧颈总动脉结扎伴低氧(6%O2)4 h侧脑室周围白质区可见坏死灶;GFAP免疫染色强度为[(6 069.13 ±458.61) OD],MBP免疫染色强度为[(15003.38 ±1 559.11) OD];左侧睁眼时间延迟.双侧颈总动脉结扎伴低氧(8%O2)30 min双侧脑室周围白质区见囊性坏死灶;左侧GFAP 免疫染色强度[(6 194.50 ±432.69) OD]增加程度最高(P <0.000 1),MBP免疫染色强度[(10119.35±735.16) OD]降低程度最显著(P<0.000 1);双侧睁眼时间延迟且双眼出现白内障改变.结论 左侧颈总动脉结扎伴低氧30 min方法更适宜轻型脑白质损伤研究;左侧颈总动脉结扎伴低氧(6%O2)4 h及 双侧颈总动脉结扎伴低氧(8%O2) 30 min更适于严重的脑室周围白质软化病例研究.

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abstractsObjective To investigate the difference among neonatal rat models of hypoxia-ischemia induced white matter injury of brain by three different methods and to provide theory basis on choosing the proper animal model for deep study on white matter injury of premature infants.Methods Three different hypoxia-ischemia methods were applied to induce brain white matter injury model of Wistar rats of postnatal 3rd day which were left carotid artery ligation followed by 6% oxygen for 30 minutes and for 4 hours respectively,and bilateral carotid artery ligation followed by 8% oxygen for 30 minutes.Compared brain pathological results of rats in different groups,changes in white matter of brain by glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) immunostaining,and changes in time of opening eyes and eyes appearance.Results Left carotid artery ligation followed by 6% oxygen for 30 minutes resulted in sparse and vague periventricular white matter without necrotic lesions,and the degree of GFAP intensity [(5 021.63 ± 358.92) OD] increase and MBP intensity [(18 488.63 ± 1 822.62) OD] decrease were lowest (P < 0.000 1),as well as the delay of opening time of the left eye.Left carotid artery ligation followed by 6% oxygen for 4 hours resulted in necrotic lesions of periventricular white matter,with the degree of GFAP intensity [(6 069.13 ± 458.61) OD] and MBP intensity [(15 003.38 ± 1 559.11) OD],and also the delay of opening time of the left eye.Bilateral carotid artery ligation followed by 8% oxygen for 30 minutes caused cystic necrosis of bilateral periventricular white matters,and the degree of GFAP intensity [(6 194.50 ±432.69) OD] increase and MBP intensity [(10 119.35 ± 735.16) OD] decrease of the left side were highest(P < 0.000 1),as well as the delay of opening time and cataract in both eyes.Conclusion Left carotid artery ligation followed by 6% oxygen for 30 minutes is more suitable for investigating mild brain white matter injury.Left carotid artery ligation followed by 6% oxygen for 4 hours and bilateral carotid artery ligation followed by 8% oxygen for 30 minutes are more proper for the investigation of severe periventricular leukemacia cases.

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