Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.
Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.
复制标题
人类肠道缺血再灌注的快速逆转通过脱落受伤的肠上皮细胞和再上皮化引起的损害。
DOI：
10.1371/journal.pone.0003428
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Buurman, Wim A.
中科院分区：
文献类型：
--
作者：
Derikx, Joep P. M.;Matthijsen, Robert A.;de Bruine, Adriaan P.;van Bijnen, Annemarie A.;Heineman, Erik;van Dam, Ronald M.;Dejong, Cornelis H. C.;Buurman, Wim A.
肠缺血-再灌注（IR）是与生理条件（例如运动、应激）和病理生理事件（例如急性肠系膜缺血、主动脉手术）相关的现象。虽然肠道IR已经在动物中进行了广泛的研究，结果仍然是不确定的，人类肠道IR的数据是稀缺的。因此，一个无害的实验模型，为人类肠道IR的发展，使我们能够澄清人类肠道IR的后遗症首次。在30例接受胰十二指肠切除术的患者中，我们利用了这样一个事实，即在此过程中，切除了可变长度的空肠。离体空肠（5cm）经受30分钟缺血，随后再灌注。肠脂肪酸结合蛋白（I-FABP）的动静脉浓度差异在整个肠段缺血之前和之后进行测量，以评估上皮细胞损伤。在缺血后和再灌注25、60和120分钟时收集组织切片，并用H&E染色，并用I-FABP和凋亡标记物M30染色。采用Bonferroni检验比较I-FABP差异。平均（SEM）I-FABP的动静脉浓度梯度横跨空肠显示迅速发展的上皮细胞损伤。I-FABP释放从缺血前的290（46）pg/ml显著增加到缺血后即刻的3，997（554）pg/ml（p<0.001），并在再灌注1小时内逐渐下降到1，143（237）pg/ml（p<0.001）。直接缺血后，肠上皮衬里是显微镜下正常的，而上皮下空间出现在绒毛尖端。然而，再灌注25分钟后，肠上皮细胞M30免疫染色观察到在绒毛尖端伴随着脱落的成熟肠上皮细胞进入管腔和I-FABP染色的损失。有趣的是，再灌注60分钟内，上皮屏障重新封闭，同时在管腔中观察到凋亡脱落上皮细胞的碎片。同时，M30免疫反应性在完整的上皮衬里中不存在。这是第一项阐明肠道IR诱导的细胞损伤和修复及其直接后果的人类研究。它揭示了一个独特的，内源性的清除机制受损的肠上皮细胞：快速脱离受损的凋亡肠上皮细胞进入管腔。这个过程之后是修复上皮连续性在一个小时内，导致正常的上皮衬里。
Intestinal ischemia-reperfusion (IR) is a phenomenon related to physiological conditions (e.g. exercise, stress) and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery). Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time. In 30 patients undergoing pancreatico-duodenectomy we took advantage of the fact that in this procedure a variable length of jejunum is removed. Isolated jejunum (5 cm) was subjected to 30 minutes ischemia followed by reperfusion. Intestinal Fatty Acid Binding Protein (I-FABP) arteriovenous concentration differences across the bowel segment were measured before and after ischemia to assess epithelial cell damage. Tissue sections were collected after ischemia and at 25, 60 and 120 minutes reperfusion and stained with H&E, and for I-FABP and the apoptosis marker M30. Bonferroni's test was used to compare I-FABP differences. Mean (SEM) arteriovenous concentration gradients of I-FABP across the jejunum revealed rapidly developing epithelial cell damage. I-FABP release significantly increased from 290 (46) pg/ml before ischemia towards 3,997 (554) pg/ml immediately after ischemia (p<0.001) and declined gradually to 1,143 (237) pg/ml within 1 hour reperfusion (p<0.001). Directly after ischemia the intestinal epithelial lining was microscopically normal, while subepithelial spaces appeared at the villus tip. However, after 25 minutes reperfusion, enterocyte M30 immunostaining was observed at the villus tip accompanied by shedding of mature enterocytes into the lumen and loss of I-FABP staining. Interestingly, within 60 minutes reperfusion the epithelial barrier resealed, while debris of apoptotic, shedded epithelial cells was observed in the lumen. At the same time, M30 immunoreactivity was absent in intact epithelial lining. This is the first human study to clarify intestinal IR induced cell damage and repair and its direct consequences. It reveals a unique, endogenous clearing mechanism for injured enterocytes: rapid detachment of damaged apoptotic enterocytes into the lumen. This process is followed by repair of the epithelial continuity within an hour, resulting in a normal epithelial lining.
登录
查看更多内容
DOI：
10.1016/s0967-2109(02)00070-4
发表时间：
2002-12-01
期刊：
CARDIOVASCULAR SURGERY
影响因子：
--
作者：
Blaisdell, FW
通讯作者：
Blaisdell, FW
影响因子：
15.9
作者：
Lee, JM;Grabb, MC;Choi, DW
通讯作者：
Choi, DW
DOI：
10.1083/jcb.124.4.619
发表时间：
1994-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Frisch SM;Francis H
通讯作者：
Francis H
影响因子：
8.8
作者：
Fukatsu, K;Sakamoto, S;Hiraide, H
通讯作者：
Hiraide, H
影响因子：
29.4
作者：
Gassler, Nikolaus;Roth, Wilfried;Kopitz, Juergen
通讯作者：
Kopitz, Juergen