缺血-再灌注致肠道细胞凋亡的特征及碱性成纤维细胞生长因子对其转归的影响

Induction of gut mucosa necrosis and apoptosis after ischemiareperfusion and the effects of fibroblast growth factor

目的：观察缺血再灌注导致肠道组织细胞凋亡发生的特征与规律，并探讨碱性成纤维细胞生长因子（ｂＦＧＦ）对细胞凋亡发生的影响和作用机制。方法：将７２只Ｗｉｓｔａｒ大鼠分成ｂＦＧＦ治疗组，生理盐水对照治疗组及假手术组３组。利用大鼠肠系膜上动脉夹闭４５分钟与再灌注４８小时模型，病理学与末端脱氧核糖转移酶介导的生物素化脱氧尿嘧啶缺刻标记技术（ＴＵＮＥＬ）方法，定量评价缺血再灌注导致大鼠肠道组织细胞凋亡与坏死的特征和ｂＦＧＦ的治疗作用。结果：肠系膜上动脉夹闭可导致肠道组织明显的缺血性损伤和细胞凋亡发生，凋亡细胞出现在肠粘膜上皮与粘膜下交界处，表现为肠粘膜上皮细胞核固缩或边缘化，部分可见凋亡小体。经ｂＦＧＦ治疗后，细胞凋亡现象可明显减轻。结论：缺血再灌注导致的肠道损伤主要来源于组织坏死与激活凋亡机制两方面，而这两方面作用均与细胞内钙离子超载密切相关；

Objective:To explore the distribution feature of apoptotic signal in gut caused by ischemiareperfusion,and the possible effect of basic fibroblast growth factor (bFGF) on reducing these alterations.Methods:Wistar rats were subjected to superior mesenteric artery occlusion (45 minutes) followed by reperfusion (6 hours).Seventytwo animals were divided into 3 groups of 24 rats each.Animals in bFGFtreated group were injected with 4 μg bFGF/rat in 0 15 ml normal saline solution containing heparin 0 1% through the jugular vein at the onset of reperfusion.In the normal saline control group,all rats received the same vehicle,but without bFGF.In shamoperated group,animals underwent the same laparotomy procedure,but without superior mesenteric artery occlusion.Histological examination and TUNEL technique were used to evaluate the results.Results:Superior mesenteric artery occlusion induce the typical tissue damage and apoptosis in the gut.Tissue necrosis and apoptosis could be observed,but the apoptotic signal could be detected only in mucosa or the borderline between mucosa and submucosa.The typical apoptotic signal included chromatin condensation,nuclear fragmentation and margination.In bFGFtreated rats,the apoptotic signal in gut was restricted and reduced significantly.Conclusions:The biological effect of apoptosis is one of the main mechanisms inducing gut damage after ischemiareperfusion injury.The mechanisms involved in reducing tissue damage by bFGF treatment may be related to its mitogenic and nonmitogenic effects in the early stage of ischemiareperfusion.