Endotoxic shock leads to apoptosis in vivo and reduces Bcl-2
Endotoxic shock leads to apoptosis in vivo and reduces Bcl-2
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DOI：
10.1097/00024382-199612000-00004
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发表时间：
1996-12-01
期刊：
影响因子：
3.1
通讯作者：
Dimmeler, S
中科院分区：
文献类型：
--
作者：
Haendeler, J;Messmer, UK;Dimmeler, S
内毒素休克导致多器官功能衰竭。目前，两种不同的细胞破坏机制受到关注：坏死和凋亡。因此，我们开始在猪中研究细胞凋亡引起的细胞死亡是否参与了这一病理生理过程。在三种不同的实验环境中，通过对组蛋白相关DNA片段具有特异性的ELISA检测DNA片段。将猪剖腹后进行内毒素输注（ETOX组，n = 6），或剖腹后不输注内毒素（ETOX组; n = 3），并与对照动物（n = 3）进行比较。与对照组动物相比，连续输注6小时内毒素（5 μ g/kg/h）导致肝脏细胞凋亡显著增加（295 +/- 11%; p <0.01），而在顺铂组中，仅检测到166 +/- 14%的轻微增加。与对照组相比，ETOX组内毒素处理动物的脾脏细胞凋亡增加150 +/- 12%（p = 0.02），而肾脏未受影响。这些结果通过琼脂糖DNA凝胶电泳得到证实。内毒素处理组动物的肝脏和脾脏中出现典型的DNA梯状条带，而肾脏中未出现。此外，免疫组化检测的DNA链断裂与末端脱氧核苷酸转移酶在肝脏切片显示染色细胞急剧增加。细胞凋亡的诱导与内毒素处理的动物中Bct-P含量降低相关。我们的研究表明，6小时的内毒素处理导致细胞凋亡的肝脏和脾脏在体内，而内毒素处理的动物的肾脏保持不受影响。这一过程可能是通过内毒素处理减少Bcl-2介导的。
Endotoxic shock results in multiple organ failure. At present, two different mechanisms of cellular destruction are of interest: necrosis and apoptosis. Therefore, we started to investigate in pigs whether cell death due to apoptosis is involved in this pathophysiological process. DNA fragments were detected by ELISA specific for histone-associated DNA fragments in three different experimental settings. Pigs were laparotomized followed by endotoxin infusion (ETOX group, n = 6), or laparotomized without endotoxin infusion (LAP group; n = 3) and compared with control animals (n = 3). 6 h of continuous endotoxin-infusion (5 mu g/kg/h) resulted in a significantly enhanced apoptosis in liver as compared with control animals (295 +/- 11%; p < .01), whereas in the LAP group, only a minor increase of 166 +/- 14% was detectable. In spleen of endotoxin-treated animals, an enhanced apoptosis of 150 +/- 12% compared with controls was shown in the ETOX group (p = .02), whereas kidney remained unaffected. These results were confirmed by agarose DNA gel electrophoresis. A typical DNA ladder was detected in liver and spleen, but not in kidney of endotoxin-treated animals. Furthermore, immunohistochemical detection of DNA strand breaks with terminal deoxynucleotidyl transferase in liver sections revealed a drastic increase of stained cells. The induction of apoptosis correlated with a reduced Bct-P content in endotoxin-treated animals. Our study demonstrates that 6 h of endotoxin treatment leads to apoptosis in liver and spleen in vivo, whereas kidney of endotoxin-treated animals remains unaffected. This process may be mediated by reduction of Bcl-2 by endotoxin treatment.