Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types
Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types
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DOI：
10.1007/s00418-005-0765-6
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发表时间：
2005-03-01
影响因子：
2.3
通讯作者：
Koji, T
中科院分区：
文献类型：
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作者：
An, SC;Hishikawa, Y;Koji, T
虽然缺血再灌注(I/R)可诱导哺乳动物小肠细胞的凋亡损伤，但其分子机制仍不清楚。采用免疫组织化学方法观察大鼠小肠缺血1h再灌注后不同时间点(0~2 4h)的细胞凋亡情况及凋亡相关蛋白Bcl2、Bax、Fas、Fas配体(FasL)、活化的caspase 3、细胞色素c的表达。TUNEL和电子显微镜检测显示，再灌流3h后，肠各部分(绒毛上皮、隐窝上皮和肠间质层)的细胞凋亡率均明显增加。此外，间质中的TUNEL阳性细胞后来被鉴定为T细胞。再灌流3h，间质中Fas、FasL及活化的caspase-3表达明显增加。在绒毛上皮细胞中，Bcl2表达一过性下降，而在隐窝上皮细胞中，Fas表达上调。最后，在I/R后，腹腔注射亮肽素(一种SH-蛋白酶抑制剂)，可显著抑制间质和隐窝上皮细胞的凋亡诱导。我们的结果表明，I/R大鼠小肠细胞凋亡的触发分子可能因细胞类型的不同而不同，使用广谱蛋白水解酶抑制剂可能会减轻肠道损伤。
Although ischemia reperfusion (I/R) induces apoptotic damage of mammalian small intestine, the molecular mechanism is largely unknown. We investigated the appearance of apoptosis at various time-points (0-24 h) of reperfusion after 1-h ischemia and the expression of various apoptosis-related proteins, such as Bcl-2, Bax, Fas, Fas ligand (FasL), activated caspase-3, and cytochrome c, immunohistochemically in rat small intestine. As assessed by TUNEL and electron microscopy, apoptotic cells were increased at 3 h of reperfusion in all intestinal parts (villous epithelium, crypt epithelium, and stroma of intestine). Moreover, the TUNEL-positive cells in the stroma were later identified as T cells. The expression of Fas and FasL as well as activated caspase-3 was markedly increased at 3 h of reperfusion in the stroma. In the villous epithelium, a transient decrease in Bcl-2 expression was found while in the crypt epithelium, Fas expression was induced. Finally, intraperitoneal injection of leupeptin (an SH-protease inhibitor) after I/R resulted in a significant inhibition of the induction of apoptosis in the stroma and crypt epithelium. Our results indicate that the triggering molecules of apoptosis in the I/R rat small intestine may vary depending on cell type and that the use of a broad-spectrum protease inhibitor may reduce intestinal damage.