Expression of interleukin-1-beta converting enzyme and its effect on cell apoptosis in cerebral ischemia-reperfusion injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Cell apoptosis is one of the important pathological changes in ischemic-reperfusion (IR) injury. As the key factor involved in cell apoptosis regulation, interleukin (IL)-iβ converting enzyme, when activated, leads to cell apoptosis via protein degradation.OBJECTIVE: To investigate the relationship between the expression of IL-1β converting enzyme and cell apoptosis in cerebral IR injury and explore the role of this enzyme in post-ischemia cell apoptosis.DESIGN: Randomized controlled experiment.MATERIALS The experiment was performed at the Center of Neuroscience of the Third Military Medical University between March 1996 and December 2000. Totally 64 adult healthy Wistar rats were randomized into two groups, namely IR group (n=56) and sham operation group (n=8). In IR group, the rats were subjected to four vessel occlusion to mimic whole brain IR injury, and reperfusion was carried out after 30 minutes of ischemia for 3, 6, 12, 24, 48, 72 hours and 7 days, respectively (8 rats at each time point). Only separation but not occlusion of the bilateral common carotid artery was performed in sham operation group.METHODS: Four rats were randomly selected from IR group at each time point and 4 from the sham operation group for immunohistochemical study and in situ hybridization, with the other 4 rats for in situ end-labeling assay.MAIN OUTCOME MEASURES: Protein and mRNA expression of ILlβ converting enzyme and neural cell apoptosis in the brain.RESULTS: Totally 64 rats were used in this study and all data were statistically analyzed. In the sham operation group, IL-1β converting enzyme protein and mRNA were expressed in small amount in most of the normal brain tissues, and their expressions were also detected in the neurons and small glial cells in IR group localized mainly in the cerebral cortex, cerebellum Purkinje's cells, hippocampal and subcortical white matters. The expression of IL-lβ converting enzyme began to increase at IR 12 hours, reaching the peak level at 48-72 hours followed by declination since 7 days after the operation. Cell apoptosis occurred 12 hours after IR (49.4±6.8) /section and peaked at 72 hours (228.6±29.8)/section, showing significant correlation with the temporal expression of IL-1β converting enzyme protein and mRNA (r=0.89, 0.68, P ＜ 0.05).CONCLUSIONS: Expressions of IL-1β converting enzyme protein and mRNA increased after IR in close correlation with post-ischemia cell apoptosis, and their temporal expression pattern supports the presumption that IL-1β converting enzyme is an important factor in cell apoptosis.Apoptosis is mostly likely to occur in the cerebral cortex, hippocampus and basal ganglion in IR injury, where IL-1β converting enzyme is highly expressed, further demonstrating that post-ischemia expression of IL-1β converting enzyme might be involved in cell apoptosis regulation.