Lauronen Jouni, Pakarinen Mikko P, Halttunen Jorma, Kuusanmäki Pekka, Haglund Caj, Paavonen Timo
Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, 00014 Helsinki, Finland.
Pediatr Surg Int. 2005 May;21(5):351-5. doi: 10.1007/s00383-005-1411-z. Epub 2005 Apr 13.
Massive small bowel resection increases ileal villus height as part of normal adaptation. However, despite no gut loss, autotransplantation of the entire small intestine also increases ileal villus height. Our aim was to test whether similar modulation of enterocyte proliferation and apoptosis underpin these comparable increases in villus height. Fifteen pigs were randomly assigned for laparotomy (n=5), 75% proximal small bowel resection (n=5), or jejunoileal autotransplantation (n=5). Eight weeks postoperatively, full-thickness small bowel sections underwent routine immunohistochemistry for cell cycle inhibitors (p53, p21, and p27), antiapoptotic Bcl-2, and proapoptotic bax. The specimens were analyzed semiquantitatively, and the number of intensively positive epithelial cells for each group was compared from 20 digital images (0.32 mm(2)/image). Compared with laparotomy, small bowel resection decreased the number of p27-positive enterocytes in both jejunum and ileum, increased the number of bax-expressing cells in ileum, but decreased the number of bax-expressing cells in jejunum. In contrast, compared with laparotomy, jejunoileal autotransplantation altered neither mucosal bax nor p27 expression. In all groups, Bcl-2 expression was similarly confined to inflammatory cells of the lamina propria, while both p53 and p21 were negative. We conclude that long-term alterations in the enterocytic expression of certain cell cycle and apoptosis markers (p27 and bax) accompany small bowel resection. These changes differ between the jejunum and the ileum and are not seen after whole small bowel autotransplantation. Therefore, increased ileal villus height after autotransplantation, despite resembling postresectional intestinal adaptation, is underpinned by different regulation of enterocyte proliferation and apoptosis.
作为正常适应性变化的一部分,大量小肠切除会增加回肠绒毛高度。然而,尽管没有肠道损失,但整个小肠的自体移植也会增加回肠绒毛高度。我们的目的是测试肠上皮细胞增殖和凋亡的类似调节是否是这些绒毛高度可比增加的基础。将15头猪随机分配接受剖腹手术(n = 5)、近端小肠75%切除(n = 5)或空肠回肠自体移植(n = 5)。术后8周,对全层小肠切片进行常规免疫组织化学检测细胞周期抑制剂(p53、p21和p27)、抗凋亡蛋白Bcl-2和促凋亡蛋白bax。对标本进行半定量分析,并从20张数字图像(0.32 mm²/图像)中比较每组强阳性上皮细胞的数量。与剖腹手术相比,小肠切除减少了空肠和回肠中p27阳性肠上皮细胞的数量,增加了回肠中bax表达细胞的数量,但减少了空肠中bax表达细胞的数量。相比之下,与剖腹手术相比,空肠回肠自体移植既未改变黏膜bax表达,也未改变p27表达。在所有组中,Bcl-2表达同样局限于固有层的炎症细胞,而p53和p21均为阴性。我们得出结论,小肠切除伴随着某些细胞周期和凋亡标志物(p27和bax)在肠上皮细胞表达中的长期改变。这些变化在空肠和回肠之间有所不同,在全小肠自体移植后未观察到。因此,尽管自体移植后回肠绒毛高度增加类似于切除术后的肠道适应性变化,但其基础是肠上皮细胞增殖和凋亡的不同调节。