Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats
Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats
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DOI：
10.1023/a:1015931128583
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发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
Gaudio, E
中科院分区：
文献类型：
--
作者：
Vetuschi, A;Latella, G;Gaudio, E
我们评估了dss诱导的结肠炎急性期和慢性期结肠黏膜的形态学改变、上皮细胞凋亡和增殖。在Sprague-Dawley大鼠中，先口服4% DSS 7天，再口服自来水7天，分别进行1、2、3个周期，诱导结肠炎。对照组老鼠只喝自来水。采用光镜和扫描电镜观察结肠黏膜形态学变化并评分。TUNEL法观察细胞凋亡，Ki-67免疫反应观察细胞增殖。免疫组化法检测促凋亡（Fas、FasL、Bax、p53）和抗凋亡（Bcl2）细胞蛋白的表达。形态学评估显示，结肠上皮病变和炎症最严重的是远端结肠，从第一个到第三个DSS周期，严重程度有增加的趋势。与对照组相比，DSS大鼠上皮细胞凋亡指数在第一个周期后增加了20倍，在第二个和第三个周期后增加了120倍；同样，促凋亡蛋白（Fas、FasL、Bax、p53）的表达指数显著升高。与对照组相比，增殖指数增加了约40至60倍，三个DSS周期之间没有差异。综上所述，dss诱导的大鼠结肠炎具有许多与人类溃疡性结肠炎相似的结构和超微结构特征，是研究上皮细胞凋亡和增殖增加的合适模型。采用该模型的进一步研究将允许检验两个假设。(1)细胞凋亡的增加可能导致上皮屏障功能的破坏，促进腔内微生物和/或抗原的粘膜侵袭。(2)在慢性结肠炎症的情况下，异常和持续的上皮细胞增生可能与结直肠癌的发生有因果关系。
We have evaluated morphologic alterations and epithelial cell apoptosis and proliferation of colonic mucosa in the acute and chronic phases of DSS-induced colitis. Colitis was induced in Sprague-Dawley rats by 7 days of 4% DSS oral administration followed by 7 days of tap water for one, two, and three cycles. Control rats receved tap water only. Morphological changes in colonic mucosa were evaluated and scored by light and scanning electron microscopy. Apoptosis was studied by TUNEL assay and cell proliferation by Ki-67 immunoreaction. The expression of both proapoptotic (Fas, FasL, Bax, p53) and antiapoptotic (Bcl2) cellular proteins was determined by immunohistochemistry. Morphologic assessment showed the most severe colonic epithelial lesions and inflammation in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats, the epithelial apoptotic index increased 20-fold after the first cycle and 120-fold after the second and third cycles compared with the controls; in the same way, the expression index of proapoptotic proteins (Fas, FasL, Bax, p53) dramatically increased. The proliferative index increased about 40 to 60-fold compared to controls, with no difference among the three DSS cycles. In conclusion, DSS-induced colitis in rats, which has many structural and ultrastructural features similar to those seen in human ulcerative colitis, is a suitable model for studying increased epithelial apoptosis and proliferation. Further studies employing this model will permitt two hypotheses to be tested. (1) Increased apoptosis may lead to a breakdown of the epithelial barrier function and facilitate the mucosal invasion of intraluminal microorganisms and/or antigens. (2) Abnormal and persistent epithelial hyperproliferation could be causally related to the development of colorectal cancers in the setting of chronic colonic inflammation.