Apopotosis Suppression in Ischemic Tolerance Phenomenon

我们探讨了白细胞介素1β转换酶(ICE)和白细胞介素1β(IL-1β)的表达在缺血耐受现象中的发病作用。雄性沙土鼠在5min致死性脑缺血前24小时进行5min亚致死性脑缺血和2min亚致死性脑缺血。动物在致死性脑缺血后第1、2、3、4或7天经心内注入4%多聚甲醛，在切片机上切开包括海马区在内的石蜡冠状切片。切片行苏木精-伊红(HE)染色，并用抗ICE或IL-1β抗血清进行免疫组织化学研究。采用原位末端标记法检测大鼠海马CA1区神经元DNA的断裂情况。HE染色切片显示，致死性脑缺血后4d，海马神经元数量明显减少，但预适应可明显抑制神经元死亡。致死性脑缺血后2~4天可见ICE免疫反应神经元，而预适应组3~4天可见散在分布的ICE免疫反应神经元。IL-1β在4d开始有较强的表达，但偶见散在表达。IL-1β阳性细胞多为小胶质细胞。TUNEL阳性神经元从3d开始显著增加，但在预适应动物中观察到的较少。提示细胞凋亡抑制机制在缺血耐受现象中的作用。

We investigated a pathogenetic role for expression in interleukin-1β converting enzyme (ICE) and interleukin-1β (IL-1β) in ischemic tolerance phenomenon. Male Mongolian gerbils were subjected to 5 min forebrain ischemia with or without 2 min sublethal ischemia 24 hours before the 5 min lethal ischemia. Animals were transcardially perfused using 4% paraformaldehyde at 1, 2, 3, 4, or 7 days after the lethal iuschemia, and paraffin-embedded coronal sections including hippocampus were cut on a microtome. Sections were stained with hematoxylin and eosin (HE) staining, and studied immunohistochemically using anti-serum against ICE or IL-1β. Furthermore TUNEL method was applied to the sections to evaluate neuronal DNA fragmentation in the hippocampal CA1 subfield. In the HE stained sections, marked reduction in number of hippocampal neurons was observed from 4 days after lethal ischemia, but the neuronal death was significantly suppressed by preconditioning. ICE immunoreactive neurons were observed from 2 to 4 days after lethal ischemia, although such neurons were scattered form 3 to 4 days in the preconditioned animals. IL-1β was strongly expressed from 4 days, but occasionally scattered in the preconditioned animals. Most of the IL-1β positive cells were microglia. TUNEL positive neurons were markedly increased from 3 days, although less observed in the preconditined animals. These suggest a role for apoptotic suppressive mechanisms in ischemic tolerance phenomenon.