外源性激活素A对高胆红素血症新生大鼠脑细胞凋亡的保护作用

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (12): 54-57.

外源性激活素A对高胆红素血症新生大鼠脑细胞凋亡的保护作用

李瑞英¹，安丽¹，赵东¹，王平²

1. 山东大学附属济南市中心医院儿科，济南 250013； 2. 山东省中医药研究院药理室，济南 250014

收稿日期:2009-05-19 出版日期:2009-12-16 发布日期:2009-12-16
通讯作者: 安丽（1967- ），女，美国哈佛医学院博士后，副教授，主要从事儿科学神经专业的研究。 Email:doctordiane@163.com
作者简介:李瑞英（1981- ），女，硕士研究生，主要从事儿科学神经专业的研究。

Protective effects of exogenous ACT A on brain cell apoptosis of neonatal rats withhyperbilirubinemia

LI Ruiying ¹ ,AN Li ¹, ZhAO Dong ¹ , WANG Ping ²

1. Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China;
2. Department of Pharmacology， Shandong Academy of Traditional Chinese Medicine, Jinan 250014, China

Received:2009-05-19 Online:2009-12-16 Published:2009-12-16

摘要/Abstract

摘要：

目的探讨外源性激活素A（ACT A）对高胆红素血症（简称高胆）新生大鼠脑细胞凋亡的保护作用。方法将96只新生7日龄Wistar大鼠随机分为正常对照组、高胆对照组、ACT A治疗Ⅰ、Ⅱ组，每组24只。采用腹腔注射胆红素溶液的方法建立高胆标准动物模型，ACT A治疗Ⅰ、Ⅱ组于造模后分别给予高（0.025?mg/L）、低（0.001?mg/L）剂量ACT A灌胃。采用重氮反应法检测各组血清和脑组织中胆红素含量，电镜下观察脑组织超微结构，采用流式细胞仪进行脑组织细胞凋亡分析。结果治疗Ⅰ、Ⅱ组神经行为异常较高胆对照组明显减轻；高胆对照组、治疗Ⅰ、Ⅱ组血清、脑组织胆红素含量均高于正常对照组（P均＜0. 01）；治疗Ⅰ、Ⅱ组血清、脑组织胆红素含量均低于高胆对照组（P均＜0.05）；治疗I组血清、脑组织胆红素含量均低于治疗Ⅱ组（P均＜0.01）。镜下观察可见，高胆对照组神经元损伤明显，各治疗组均有不同程度的修复；流式细胞术结果表明，在造模后12?h,高胆对照组、治疗Ⅰ、Ⅱ组脑组织凋亡细胞数均值高于正常对照组（P均＜0.001），治疗Ⅰ、Ⅱ组脑组织凋亡细胞数均值低于高胆对照组（P均＜0.05），治疗Ⅰ组脑组织凋亡细胞数低于治疗Ⅱ组（P＜0.001）。结论外源性ACT A可明显减少高胆模型鼠体内胆红素的蓄积，有效抑制高胆模型鼠脑细胞凋亡，对高胆所致脑损伤具有保护作用。

关键词: 外源性激活素 A；高胆红素血症；流式细胞术；细胞凋亡；大鼠，Wistar

Abstract:

To explore the protective effects of exogenous activin A (ACT A) on brain cell apoptosis of neonatal rats with hyperbilirubinemia. Methods96 sevendayold Wistar rats were randomly divided into the normal control group(C0), the hyperbilirubinemia control group (C1) and the ACT A treatment Ⅰ and Ⅱ groups (T1, T2). The hyperbilirubinemia control group and both ACT A treatment groups were intraperitoneally(I.P.) injected with bilirubin. The ACT A treatment Ⅰ and Ⅱ groups were orally given a high or low dose of ACT A respectively right after I.P. Bilirubin contents (TB) in the serum and brain tissues were measured by Diazo reaction, brain tissue ultrastructure was observed under an electron microscope, and brain tissue apoptosis analysis was done by flow cytometry. ResultsThe neurobehavioral abnornalities of the C1 group was significantly more severe than those of the T1 and T2 groups. The mean TB in both serum and brain tissues of the C1, T1, and T2 groups was higher than that of the C0 group（P all＜0.01）. The mean TB of T1 and T2 in both serum and brain tissues was lower than that of the C1 group（P all ＜0.05）. The mean TB of the T1 group in both serum and brain tissues was lower than that of the T2 group（P all ＜0.01）. Under an electron microscope, the neurons in the C1 group were significantly damaged. Plerosis of ultramicrostructure of different degrees was found in the T1 and T2 groups compared with the C1 group. The results of flow cytometry showed that the mean value of brain cell apoptosis at 12?h in the C1, T1, and T2 groups was higher than that of the C0 group (P all ＜0.001）. The mean value of brain cell apoptosis at 12?h in the T1 and T2 groups was lower than that of the C1 group（P all ＜0.05）. The mean value of the brain cell apoptosis at 12?h in the T1 group was lower than that of the T2 group (P＜0.001）. ConclusionExogenous ACT A can significantly reduce the accumulation of bilirubin, depress brain cell apoptosis, and protect the brain tissue of neonatal rats with hyperbilirubinemia.

Key words: Exogenous activin A; Hyperbilirubinemia; Flow cytometry; Apoptosis;Rats, Wistar

中图分类号:

R395.2

李瑞英1，安丽1，赵东1，王平2. 外源性激活素A对高胆红素血症新生大鼠脑细胞凋亡的保护作用[J]. 山东大学学报(医学版), 2009, 47(12): 54-57.

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