Coloproctology Unit of the Surgery Department, University of Campinas (UNICAMP), Medical School, São Paulo, Brazil.
J Transl Med. 2010 Jan 29;8:11. doi: 10.1186/1479-5876-8-11.
Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP.
Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP.
Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot.
Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups.
Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.
回肠贮袋肛管吻合术（IPAA）是治疗溃疡性结肠炎（UC）和家族性腺瘤性息肉病（FAP）伴直肠多发息肉患者的首选手术方法。贮袋炎是 UC 患者 IPAA 后较为常见的并发症之一；然而，在 FAP 中则较为少见。
评估 UC 和 FAP 患者回肠贮袋内镜和组织学正常黏膜中的促凋亡活性。
研究了 18 例（UC 患者 9 例，FAP 患者 9 例）接受全直肠结肠切除术后 J 袋患者。从贮袋和正常回肠黏膜获取活检。将标本迅速冷冻，通过蛋白提取物的免疫印迹和免疫组化分析测定 Bax 和 Bcl-2 的表达。通过免疫沉淀和免疫印迹评估 FADD、Caspase-8、APAF-1 和 Caspase-9。
UC 患者 Bax 和 APAF-1、Caspase-9 的蛋白水平明显高于 FAP 患者，但与对照组相似。Bcl-2 和 FADD、Caspase-8 的表达在各组之间相似。Bax 的免疫组化显示 FAP 中的免疫反应强度低于 UC 和对照组。各组的 Bcl-2 免疫染色相似。
在所有应用的方法中，FAP 患者的促凋亡蛋白水平较低，即使在组织学分析中没有临床和内镜贮袋炎和异型增生的情况下也是如此。这些发现可能解释了 UC 患者凋亡上调的趋势，导致这些患者发生贮袋炎的比率较高，这可能与炎症组织中的黏膜萎缩有关。然而，FAP 患者的黏膜促凋亡活性较低，这可能解释了该综合征中细胞更替率低和腺瘤存在的倾向。
