基因和性别改变心脏骤停和心肺复苏的转归
尽管40年来不断探索关于心脏停跳和心肺复苏(CPR),临床成果仍然很贫乏。以前许多这方面的研究一直采用发展新的心肺复苏方法学或药理学形式，然而现在，我们需要用巧妙的基础科学和分子遗传学方法来提高对于CPR过程中损伤的临床机制的理解，从而发展出新的治疗方法。多聚聚合酶(PARP)是一种含量丰富的核酶，它有助于维持神经原细胞及其他细胞类型的染色体组的完整性。使用药理因子抑制PARP或者通过PARP敲除导致PARP缺陷都可以减少局部缺血后的损伤，然而心肺复苏后PARP是否受累尚未可知。
我们评价了PARP与其野生型对照组相比心肺复苏的效果。组织学结果通过分析苏木精和伊红染色的脑组织切片得出，损伤的评定是通过计算某一受累区域中受损伤神经元占全部神经元的百分率得出的。我们发现受损神经元PARP的百分数在所有被检测的大脑的三个区域均有减少：海马(背侧的CA1区)，后部尾壳核，前部尾壳核。在CA1区从野生型到PARP受损神经元百分值减少了33%，在后尾状核减少了47%，在前尾状核减少了40%。我们同时还发现与其对照组野生型(C57B16)相对比，带有正调节超氧化物歧化酶动物的尾壳核中损伤细胞的百分数下降35%。
, 百拇医药
最后，我们检验了心肺复苏的结果是否存在性别差异。我们发现正常雌性老鼠比雄性老鼠损伤细胞的百分数低53%。当雌性老鼠卵巢切除后这种性别差异消失了，但当给切除卵巢的雌性老鼠用雌激素后这种性别差异重新出现。上述资料证实基因和性别都是心肺复苏后果的重要决定因素。因此基因和性别代表了改变心肺复苏结果治疗目标的两个新领域。
Genes and Gender Alter Outcome From Cardiac Arrest and Cardiopulmonary Resuscitation
Richard J. Traystman, PhD, Julia Kofler, MD, Ruediger Noppens, MD, Patricia D. Hurn, PhD
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code L335, Portland, OR 97239 USA
, http://www.100md.com
Despite four decades of research concerning cardiac arrest/cardiopulmonary resuscitation (CPR), clinical outcome remains poor. Much of this research has taken the form of developing new methodological or pharmacological approaches to CPR. Now, however, novel basic science and molecular genetic approaches to CPR are needed to improve our understanding of critical mechanisms of injury during CPR to develop new therapeutic interventions. Poly (ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme which helps maintain genomic integrity in neurons and other cell types. Inhibition of PARP with pharmacological agents or PARP deficiency via PARP knockout (-/-) animals reduces injury after focal ischemia, but the involvement of PARP after CPR is unknown. We evaluated the effect of CPR in PARP-/- compared to their wild-type controls (SV129). Tissue outcome was analyzed in H and E stained brain sections and damage was assessed by calculating the percentage of injured neurons referred to the total number of neurons in an area. We found that the percent of injured neurons was reduced in PARP-/- in all three areas of brain examined: hippocampus (dorsal CA1), posterior caudoputamen and anterior caudoputamen. The % injured neurons was reduced from wild-type to PARP-/- by 33% in CA1, 47% in posterior caudoputamen and 40% in anterior caudoputamen. We also found that there was a reduction (35%) in the % of injured cells in caudoputamen in animals with upregulated superoxide dismutase (SOD+) compared with their wild-type controls (C57Bl6). Finally, we examined whether there exists a gender difference in outcome from CPR and found that the % injured cells are less (53%) in normal female than male mice. This gender difference disappeared when the females were ovariectomized, but reappeared when the ovariectomized animals were administered estrogen. These data demonstrate that both genes and gender may be important factors in determining outcome from CPR. Thus genes and gender may represent two new areas for therapeutic targets to alter outcome from CPR.
Supported by: NS 20020 and NS 46072, http://www.100md.com(不详)
我们评价了PARP与其野生型对照组相比心肺复苏的效果。组织学结果通过分析苏木精和伊红染色的脑组织切片得出，损伤的评定是通过计算某一受累区域中受损伤神经元占全部神经元的百分率得出的。我们发现受损神经元PARP的百分数在所有被检测的大脑的三个区域均有减少：海马(背侧的CA1区)，后部尾壳核，前部尾壳核。在CA1区从野生型到PARP受损神经元百分值减少了33%，在后尾状核减少了47%，在前尾状核减少了40%。我们同时还发现与其对照组野生型(C57B16)相对比，带有正调节超氧化物歧化酶动物的尾壳核中损伤细胞的百分数下降35%。
, 百拇医药
最后，我们检验了心肺复苏的结果是否存在性别差异。我们发现正常雌性老鼠比雄性老鼠损伤细胞的百分数低53%。当雌性老鼠卵巢切除后这种性别差异消失了，但当给切除卵巢的雌性老鼠用雌激素后这种性别差异重新出现。上述资料证实基因和性别都是心肺复苏后果的重要决定因素。因此基因和性别代表了改变心肺复苏结果治疗目标的两个新领域。
Genes and Gender Alter Outcome From Cardiac Arrest and Cardiopulmonary Resuscitation
Richard J. Traystman, PhD, Julia Kofler, MD, Ruediger Noppens, MD, Patricia D. Hurn, PhD
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code L335, Portland, OR 97239 USA
, http://www.100md.com
Despite four decades of research concerning cardiac arrest/cardiopulmonary resuscitation (CPR), clinical outcome remains poor. Much of this research has taken the form of developing new methodological or pharmacological approaches to CPR. Now, however, novel basic science and molecular genetic approaches to CPR are needed to improve our understanding of critical mechanisms of injury during CPR to develop new therapeutic interventions. Poly (ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme which helps maintain genomic integrity in neurons and other cell types. Inhibition of PARP with pharmacological agents or PARP deficiency via PARP knockout (-/-) animals reduces injury after focal ischemia, but the involvement of PARP after CPR is unknown. We evaluated the effect of CPR in PARP-/- compared to their wild-type controls (SV129). Tissue outcome was analyzed in H and E stained brain sections and damage was assessed by calculating the percentage of injured neurons referred to the total number of neurons in an area. We found that the percent of injured neurons was reduced in PARP-/- in all three areas of brain examined: hippocampus (dorsal CA1), posterior caudoputamen and anterior caudoputamen. The % injured neurons was reduced from wild-type to PARP-/- by 33% in CA1, 47% in posterior caudoputamen and 40% in anterior caudoputamen. We also found that there was a reduction (35%) in the % of injured cells in caudoputamen in animals with upregulated superoxide dismutase (SOD+) compared with their wild-type controls (C57Bl6). Finally, we examined whether there exists a gender difference in outcome from CPR and found that the % injured cells are less (53%) in normal female than male mice. This gender difference disappeared when the females were ovariectomized, but reappeared when the ovariectomized animals were administered estrogen. These data demonstrate that both genes and gender may be important factors in determining outcome from CPR. Thus genes and gender may represent two new areas for therapeutic targets to alter outcome from CPR.
Supported by: NS 20020 and NS 46072, http://www.100md.com(不详)