外源性激活素A对高胆红素血症新生大鼠脑细胞凋亡的抑制作用  

Depressive effects of exogenous ACT A on the brain cell apoptosis of neonatal rats with hyperbilirubinemia

作　　者：安丽[1] 李瑞英[1] 赵东[1] 王平[2] 

机构地区：[1]山东大学附属济南市中心医院儿科,山东济南250013 [2]山东省中医药研究院药理室,山东济南250014

出　　处：《中国儿童保健杂志》2009年第6期670-672,共3页Chinese Journal of Child Health Care

基　　金：山东省自然科学基金项目(Y2006C37)

摘　　要：【目的】探讨外源性激活素A(activin A,ACT A)对高胆红素血症(简称高胆)新生大鼠脑细胞凋亡的抑制作用。【方法】将48只新生7日龄Wistar大鼠随机分为4组,即正常对照组、高胆对照组、ACT A治疗组Ⅰ、Ⅱ。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治疗组Ⅰ、Ⅱ于造模后分别灌胃给予高、低剂量ACT A。于不同时间点(1、6、12、24、487、2 h)采集标本,通过检测各组血清和脑组织中胆红素含量,电镜观察脑组织超微结构,流式细胞仪做脑组织细胞凋亡分析,经统计学处理,研究外源性ACT A对高胆模型鼠脑细胞凋亡的影响。【结果】治疗组Ⅰ、Ⅱ神经行为异常较高胆对照组明显减轻;各组血清胆红素浓度于造模后6 h达峰值,脑组织胆红素含量于造模后12h达峰值;高胆对照组、治疗组Ⅰ、Ⅱ各时间点血清、脑组织胆红素含量均高于正常对照组(P<0.001或<0.01);治疗组Ⅰ、Ⅱ各时间点血清、脑组织胆红素含量均低于高胆对照组(血清:P<0.001或<0.05;脑组织:P<0.001或<0.01);治疗组Ⅰ各时间点血清、脑组织胆红素含量均低于治疗组Ⅱ,各时间点均值比较差异有显著性(P均<0.01)。电镜下,高胆模型组神经元损伤明显,各治疗组均有不同程度的修复;流式细胞术结果表明,高胆对照组、治疗组Ⅰ、Ⅱ在造模后12 h脑组织凋亡细胞数均值高于正常对照组,治疗组Ⅰ、Ⅱ在造模后12 h脑组织凋亡细胞数均值低于高胆对照组,治疗组Ⅰ在造模后12 h脑组织凋亡细胞数低于治疗组Ⅱ。【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,且呈现剂量依从性。[Objective] To explore the depressive effects of exogenous activin A （ACT A） on the brain cell apoptosis of neonatal rats with hyperbilirubinemia. [Methods] Totally 48 seven day-old Wistar rats were randomly divided into 4 groups： normal control group （Co）, hyperbilirubinemia control group （C1） and ACT A treatment group Ⅰ and Ⅱ （T1 , T2 ）. Hyperbilirubinemia control group and both ACT A treatment groups were injected bilirubin intraperitoneally （I. P. ）. The ACT A treatment group Ⅰ and Ⅱ were respectively given orally high and low dose of ACT A rightly after I.P. The specimens were collected respectively at different time points. The bilirubin contents （TB） in the serum and brain tissue were measured, brain tissue ultrastructure was observed with electron microscope, brain tissue apoptosis analysis was done with flow cytometry. All data was treated by statistics. [Results] The neurobehavioral abnormal of C1 group was severer significantly than those of T1 and T2 groups. The TB reached a peak at 6 h in serum and 12 h in brain tissue after I. P.of each group. The mean TB of each time point of C1 , T1, T2 groups in both serum and brain tissue were higher than those of C0 group（P〈0. 001 or 〈0.01 ）. The mean TB of each time point of T1, T2 in both serum and brain tissue were lower than those of C1 group（Serum：P〈0. 001 or P〈0.05; Brain tissue：P〈0. 001 or P〈0.01）. The mean TB of each time point of T1 group in both serum and brain tissue were lower than those of T2 group（P〈0.01 ）. Under the electron micro-scope,the neuron in C1 group was damaged significantly. Plerosis of uhramicrostructurein on different degrees was found in T1 and T2 groups compared with the C1 group. The results of flow cytometry showed that the mean value of the brain cell apoptosis at 12 h in C1 , T1, T2 groups were higher than those of Co group. T1 and T2 groups were lower than those of C1 group. The mean value of the brain cell apoptosis at 12 h in T1 group was lower than those of T2

关 键 词：外源性激活素A 高胆红素血症 细胞凋亡 新生大鼠 

分 类 号：R95-33[医药卫生—药学]