目的研究血晶素对全脑缺血再灌注W istar大鼠脑保护作用及机制。方法成功建立成年W istar大鼠全脑缺血再灌注模型后,于全脑缺血10 m in再灌注24、48、72 h 3个时相点观察缺血再灌注对大鼠脑组织血红素加氧酶-1(hem e oxygenase-1,HO-1)...目的研究血晶素对全脑缺血再灌注W istar大鼠脑保护作用及机制。方法成功建立成年W istar大鼠全脑缺血再灌注模型后,于全脑缺血10 m in再灌注24、48、72 h 3个时相点观察缺血再灌注对大鼠脑组织血红素加氧酶-1(hem e oxygenase-1,HO-1)蛋白表达及皮质神经元的作用及变化规律;并于模型成功建立后5 m in,1、2 d侧脑室内注射25mg/kg的血晶素,观察血晶素对缺血再灌注大鼠脑HO-1蛋白表达及皮质神经元的影响。结果大鼠脑组织HO-1蛋白表达在全脑缺血10 m in再灌注48 h达高峰(P<0.05);血晶素可促进脑HO-1蛋白表达(P<0.05),并减轻了全脑缺血再灌注所导致的皮质损害。结论血晶素对缺血再灌注大鼠脑缺血有保护作用,其可能的机制是通过上调脑HO-1蛋白表达,启动一系列的内源性的神经保护机制来发挥脑保护作用。展开更多
Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal ...Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal and appear to die from anemia owing to defects in definitive erythropoiesis. However, the underlying molecular mechanisms of N-CoR- mediated erythroid differentiation are largely unknown. Using the human erythroleukemic K562 cell line, which can be chemically induced to differentiate into either erythroid or megakaryocytic lineages depending on the inducers used, we have investigated the role of N-CoR in erythroid differentiation. We show that knockdown of N-CoR either transiently （siRNA） or permanently （shRNA） impairs the cytosine arabinoside （Ara-C）- but not hemin-induced erythroid differ- entiation of K562 cells. RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase （ALA-S2）, a key enzyme involved in heme biosynthesis. Furthermore, the amount of N-CoR proteins increases significantly during Ara-C-induced K562 differentiation, apparently through a post-transcriptional mechanism. Consistent with the data from N-CoR-null mice, N-CoR is not required for the differentiation of K562 cells into megakaryocytic lineages, induced by phorbol 12-myristate 13-acetate. Thus, our in vitro study confirms a role for N-CoR in erythroid differentiation and reveals for the first time that N-CoR is required for the induction of a key enzyme involved in heme synthesis.展开更多
文摘目的研究血晶素对全脑缺血再灌注W istar大鼠脑保护作用及机制。方法成功建立成年W istar大鼠全脑缺血再灌注模型后,于全脑缺血10 m in再灌注24、48、72 h 3个时相点观察缺血再灌注对大鼠脑组织血红素加氧酶-1(hem e oxygenase-1,HO-1)蛋白表达及皮质神经元的作用及变化规律;并于模型成功建立后5 m in,1、2 d侧脑室内注射25mg/kg的血晶素,观察血晶素对缺血再灌注大鼠脑HO-1蛋白表达及皮质神经元的影响。结果大鼠脑组织HO-1蛋白表达在全脑缺血10 m in再灌注48 h达高峰(P<0.05);血晶素可促进脑HO-1蛋白表达(P<0.05),并减轻了全脑缺血再灌注所导致的皮质损害。结论血晶素对缺血再灌注大鼠脑缺血有保护作用,其可能的机制是通过上调脑HO-1蛋白表达,启动一系列的内源性的神经保护机制来发挥脑保护作用。
文摘Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal and appear to die from anemia owing to defects in definitive erythropoiesis. However, the underlying molecular mechanisms of N-CoR- mediated erythroid differentiation are largely unknown. Using the human erythroleukemic K562 cell line, which can be chemically induced to differentiate into either erythroid or megakaryocytic lineages depending on the inducers used, we have investigated the role of N-CoR in erythroid differentiation. We show that knockdown of N-CoR either transiently （siRNA） or permanently （shRNA） impairs the cytosine arabinoside （Ara-C）- but not hemin-induced erythroid differ- entiation of K562 cells. RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase （ALA-S2）, a key enzyme involved in heme biosynthesis. Furthermore, the amount of N-CoR proteins increases significantly during Ara-C-induced K562 differentiation, apparently through a post-transcriptional mechanism. Consistent with the data from N-CoR-null mice, N-CoR is not required for the differentiation of K562 cells into megakaryocytic lineages, induced by phorbol 12-myristate 13-acetate. Thus, our in vitro study confirms a role for N-CoR in erythroid differentiation and reveals for the first time that N-CoR is required for the induction of a key enzyme involved in heme synthesis.
