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目的测定肿瘤坏死因子样凋亡弱诱导因子(TWEAK)/成纤维细胞生长诱导因子14(Fn14)在克罗恩病(CD)患者血清及结肠组织中的表达,初步探讨TWEAK/Fn14是否可作为预测CD肠壁纤维化的指标之一。方法收集67例CD患者和33例健康对照者的外周血标本,采用ELISA法检测血清TWEAK水平。同时收集29例接受手术治疗的CD患者结肠手术标本和15例接受手术治疗的结肠癌患者手术标本中正常结肠组织,采用免疫组化法测定结肠组织中TWEAK、Fn14的表达水平。采用免疫荧光法计数结肠组织中Fn14、α-平滑肌肌动蛋白(α-SMA)双阳性细胞数。结果 CD患者血清TWEAK的表达水平较对照组升高(P<0.01),其中合并肠狭窄或肠梗阻的患者升高尤为明显(P<0.05)。血清TWEAK水平与结肠手术史(r=0.295,P=0.015)、肠狭窄(r=0.290,P=0.017)及肠梗阻(r=0.453,P=0.000 1)相关。ROC分析提示TWEAK用于预测CD并发肠壁狭窄的曲线下面积为0.67(95%CI:0.54~0.80,P=0.020)。免疫组化结果显示合并肠梗阻的CD患者结肠组织中TWEAK和Fn14的表达水平高于无肠梗阻的CD患者和对照组(P<0.05)。免疫荧光结果显示Fn14和α-SMA双阳性的细胞数量在伴有肠梗阻的CD患者结肠黏膜中明显增加(P<0.05)。结论 TWEAK/Fn14通路可能在CD肠壁纤维化中扮演着重要角色。
Objective To determine the expression of tumor necrosis factor-like weak inducing factor (TWEAK) / fibroblast growth-inducing factor 14 (Fn14) in serum and colon of patients with Crohn’s disease (CD) and to explore whether TWEAK / Fn14 can be used as Predict CD one of the indicators of intestinal fibrosis. Methods Peripheral blood samples of 67 CD patients and 33 healthy controls were collected. The level of serum TWEAK was measured by ELISA. At the same time, we collected colorectal surgical specimens from 29 patients undergoing surgical treatment and normal colon tissues from 15 surgical specimens of colon cancer patients. The expression of TWEAK and Fn14 in colonic tissues was detected by immunohistochemistry. Immunofluorescence method was used to count the number of double positive cells of Fn14 and α-smooth muscle actin (α-SMA) in colon tissue. Results The serum level of TWEAK in patients with CD was higher than that in the control group (P <0.01), especially in patients with intestinal stenosis or intestinal obstruction (P <0.05). The level of serum TWEAK was correlated with the history of colon surgery (r = 0.295, P = 0.015), intestinal stenosis (r = 0.290, P = 0.017) and intestinal obstruction (r = 0.453, P = 0.000 1). ROC analysis suggested that the area under the curve of TWEAK for prediction of CD complicated intestinal wall stenosis was 0.67 (95% CI: 0.54-0.80, P = 0.020). The results of immunohistochemistry showed that the expressions of TWEAK and Fn14 in colonic tissue of patients with intestinal obstruction were significantly higher than those without intestinal obstruction (P <0.05). Immunofluorescence results showed that the number of Fn14 and α-SMA double positive cells in colonic mucosa of patients with intestinal obstruction was significantly increased (P <0.05). Conclusion The TWEAK / Fn14 pathway may play an important role in CD intestinal fibrosis.