大鼠实验性肾缺血/再灌注引起肾小管上皮细胞凋亡及其与Bcl-2,Fas/FasL表达变化的关系

目的：探讨大鼠实验性肾缺血再灌注引起肾脏损伤、肾小管上皮细胞凋亡情况及其与Bcl—2，Fas／FasL表达变化的关系．方法：建立大鼠肾缺血再灌注损伤模型，在不同时间点处死动物取肾组织石蜡包埋切片，HE染色分析肾组织病理损伤程度，用TUNEL法标记检测肾小管上皮细胞凋亡的变化，SABC免疫组化方法检测Bcl—2，Fas与FasL蛋白表达的变化．结果：缺血再灌注后肾组织的病理损伤主要发生在肾小管，肾小管上皮细胞凋亡指数增加，且随缺血再灌注时间延长而进一步上升，48h达高峰(P＜0．05).Bcl—2蛋白在对照组呈弱阳性表达，缺血30min，60min后再灌注0h有少量表达，再灌注24，48及72h呈阳性表达，48h达高峰(P＜0.05)，并以远曲小管为主．Fas，FasL蛋白在对照组呈阴性表达，缺血30，60min后再灌注0h有少量表达，再灌注24，48及72h呈阳性表达，以72h时达高峰(P＜0.05)，多表达在远曲小管．HE染色可见肾缺血再灌注后各组均有不同程度的肾小管上皮组织片状坏死灶，以近曲小管为主，坏死灶周围有炎性细胞浸润．结论：肾缺血再灌注可诱导肾小管上皮细胞凋亡，Bcl—2，Fas／FasL系统可能在肾小管上皮细胞凋亡过程中发生着重要的调控作用．

Relationship between apoptosis of renal tubular epithelial cells and the change of expression of Bcl-2 and Fas/FasL proteins in rats after renal ischemia/reperfusion injury

AIM: To investigate the changes of the expression of Bcl 2 and Fas/FasL proteins and apoptosis in rat kidneys after ischemia/reperfusion and their relations to renal injury. METHODS: Renal ischemia/reperfusion injury models of rat were established and SABC immunohistochemical methods were used to detect the changes of expression of Bcl 2 and Fas/FasL proteins. Pathomorphological changes of renal ischemia/reperfusion injury were also observed and the occurrence of apoptosis was detected by TUNEL method. RESULTS: The pathological changes mainly occurred in the tubular epithelial cells of rat kidneys. The apoptosis index and the expression of Bcl 2 proteins increased in the kidneys of ischemia/reperfusion group, gradually upregulated with the duration of ischemia/reperfusion and peaked at 48 h of reperfusion ( P < 0.05). Bcl 2 mainly expressed in renal distal convoluted tubules and the expression was weak positive in control group. Fas/FasL peaked at 72 h of reperfusion ( P <0.05) and was negatively expressed in the control group. Local necrosis and inflammatory cell infiltration surrounding the infracted area of ischemia/reperfusion groups were found by HE stain. The necrosis mainly occurred around the proximal convoluted tubules. CONCLUSION: These results suggest that ischemia/reperfusion injury can induce apoptosis in rat kidneys and Bcl 2 and Fas/FasL proteins may be involved in the process of renal ischemia/reperfusion injury.