Study on the repairation of intestinal mucosal barrier by infliximab in patients with Crohn′s disease / 中华消化杂志

ABSTRACT

Objective:To explore the role of infliximab (IFX) in the repairation of intestinal mucosal barrier in Crohn′s disease (CD).Methods:From January 2018 to October 2019, in Shanghai Tenth People′s Hospital, 382 CD patients were selected. All the patients were treated with IFX. And 103 individuals who underwent colonoscopy were selected as healthy control group. The general clinical data, fasting blood samples and intestinal mucosa tissue samples of CD patients and healthy controls were collected. The body mass index (BMI), hemoglobin, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and relative inflammation factors, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 and IL-17A, and their mRNA expression levels were detected. Crohn′s disease activity index (CDAI) and simplified endoscopic score for Crohn′s disease (SES-CD) were used to evaluate the disease activity of CD patients. The expression levels of occudin, claudin-1, zonula occluden-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were measured by Western blotting. The intestinal mucosal epithelial cells were observed by transmission electron microscope. T test was used for statistical analysis. Results:Before treatment, BMI, and hemoglobin and albumin levels of CD patients were all lower than those of healthy control group ((18.3±1.8) kg/m 2 vs. (20.2±1.2) kg/m 2, (95.3±8.4) g/L vs. (129.2±5.7) g/L, (33.2±5.4) g/L vs. (50.3±3.2) g/L), and the differences were statistically significant ( t=3.457, 5.342 and 2.674, all P<0.05). After treatment the BMI and hemoglobin levels of CD patients were higher than those before treatment ((19.5±2.1) kg/m 2 vs. (18.3±1.8) kg/m 2, (117.2±10.3) g/L vs. (95.3±8.4) g/L), and the CRP level, CDAI score and SES-CD score were lower than those before treatment ((16.3±2.3) mg/L vs. (47.2±9.3) mg/L, 113.2±12.5 vs. 245.2±23.5, 5.0±2.1 vs. 10.0±4.3), and the differences were statistically significant ( t=2.090, 2.339, 2.432, 6.345 and 5.234, all P<0.05). The expression levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A and their mRNA levels of healthy control group were lower than those of CD patients before treatment ((1.1±0.4) ng/L vs.(158.2±38.3) ng/L, (3.2±0.8) ng/L vs. (28.3±13.4) ng/L, (2.7±1.3) ng/L vs. (3.3±2.4) ng/L, (5.2±0.3) ng/L vs. (16.3±7.4) ng/L, (16.3±6.3) ng/L vs. (18.9±10.2) ng/L, (10.5±2.3) ng/L vs. (38.5±11.2) ng/L; 1.00±0.00 vs. 4.68±0.34, 7.83±0.32, 1.25±0.46, 8.36±0.44, 2.01±0.89 and 6.83±0.53, respectively), and the differences were statistically significant ( t=2.345, 6.456, 3.008, 4.009, 7.045, 10.223, 8.345, 11.235, 1.114, 12.334, 5.304 and 5.678, all P<0.05). After treatment the TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A expression levels and their mRNA levels of CD patients were lower than those before treatment ((106.4±29.9) ng/L vs. (158.2±38.3) ng/L, (25.7±10.8) ng/L vs. (28.3±13.4) ng/L, (2.9±1.7) ng/L vs. (3.3±2.4) ng/L, (15.4±4.2) ng/L vs. (16.3±7.4) ng/L, (17.2±8.7) ng/L vs. (18.9±10.2) ng/L, (29.9±12.7) ng/L vs. (38.5±11.2) ng/L, 2.45±0.21 vs. 4.68±0.34, 3.75±0.18 vs. 7.83±0.32, 1.09±0.22 vs. 1.25±0.46, 3.78±0.21 vs. 8.36±0.44, 1.67±0.33 vs. 2.01±0.89, 2.96±0.11 vs. 6.83±0.53), and the differences were statistically significant ( t=9.345, 2.456, 2.334, 2.090, 3.009, 8.345, 4.567, 6.445, 2.046, 7.774, 3.008 and 8.867, all P<0.05). The results of Western blotting showed that the expression levels of occudin, claudin-1, ZO-1 and JAM-A in the intestinal mucosa of CD patients before treatment were lower than those of the healthy control group (0.21±0.03 vs. 1.00±0.02, 0.17±0.07 vs. 1.00±0.01, 0.16±0.06 vs. 1.00±0.04, 0.26±0.08 vs. 1.03±0.04). After treatment the expression levels of occudin, claudin-1, ZO-1 and JAM- A mRNA in the intestinal mucosa of CD patients were higher than those before treatment (0.77±0.08 vs. 0.21±0.03, 0.69±0.08 vs. 0.17±0.07, 0.78±0.09 vs. 0.16 ±0.06, 0.72±0.07 vs. 0.26±0.08), and the differences were statistically significant ( t=4.567, 6.346, 5.557, 8.456, 9.678, 8.671, 10.456 and 7.456, all P<0.05). Conclusions:IFX can effectively relieve the disease activity and improve the nutritional status of CD patients. IFX maintains the expression of intestinal epithelial tight junction protein by reducing inflammatory response, and repairs the intestinal mucosal barrier of CD patients.