To research the function of connective tissue growth factor (CTGF) monoclonal antibody (mAb) on dextran sodium sulfate (DSS) induced intestinal wall fibrosis in mice with chronic colitis.

Mouse chronic colitis model was induced by free drinking dextran sulfate sodium(DSS). Twenty-five Balb/c female mice were randomly divided into 5 groups with 5 mice in each group. One group was the blank control group which drinking distilled water for 36 days, and the other four groups drank 2.5% DSS solution for 4 days and distilled water for 5 days, and the cycle was repeated until the 36th day. At the same time, the four groups were given placebo (20 mg/kg non-specific human IgG) and different concentrations of CTGF monoclonal antibody (10 mg/kg, 20 mg/kg, 40 mg/kg) by intraperitoneal injection twice a week from the first day. The Clinical manifestations, feces characteristics, body weight, feces occult blood of mice were observed every day, and the disease activity index (DAI) score was given. On the 36th day, the colons of mice were obtained for histopathological scoring with HE staining. Collagen and α-smooth muscle actin (α-SMA) contents were detected by Masson staining andα-SMA immunohistochemical staining, and the expression levels of α-SMA, procollagen type Ⅰ (PC-Ⅰ) and CTGF mRNA in colonic tissues of mice were detected by real-time fluorescence quantitative PCR (RT-PCR).

Compared with the blank group, the DAI score, pathological score, collagen content and α-SMA content in the placebo group were significantly increased (P=0.0005, P=0.0133, P＜0.0001, P=0.0207), and the mRNA expression levels of α-SMA, PC-Ⅰ and CTGF were significantly increased (P=0.0086, P=0.0109, P=0.0046). Compared with the placebo group, the DAI scores of the 10 mg/kg and 40 mg/kg mAb groups were significantly lower (P=0.0111, P=0.0011). The pathological scores of the 20 mg/kg mAb group were significantly lower than those of the placebo group (P=0.0216), and there was no significant difference among the groups with different concentrations of mAb (P=0.4004). Compared with placebo group, collagen content in 10 mg/kg, 20 mg/kg and 40 mg/kg mAb groups was significantly decreased (P=0.0011, P=0.0006, P=0.0002), and there was no statistical difference among different concentration groups (P=0.3762). Compared with placebo group, α-SMA content in 40 mg/kg mAb group was significantly decreased (P=0.0281), but there was no significant difference among different concentration groups (P=0.0766). The expression levels of PC-Ⅰ and CTGF mRNA in the 10 mg/kg mAb group were significantly lower than those in the placebo group (P=0.0421, P=0.0296). The expression levels of α-SMA, PC-Ⅰ and CTGF mRNA in the 20 mg/kg mAb group were significantly lower than those in the placebo group (P=0.0425, P=0.0233, P=0.0107). The expression levels of α-SMA, PC-Ⅰ and CTGF mRNA in the 40 mg/kg mAb group were significantly lower than those in the placebo group (P=0.0087, P=0.0031, P=0.0024). The expression level of α-SMA mRNA in the 40 mg/kg mAb group was significantly lower than that in the 10 mg/kg mAb group (P=0.0434).

Chronic intestinal inflammation is accompanied by the formation of fibrosis. Anti-CTGF mAb can reduce the mRNA expression of α-SMA, PC-Ⅰ and CTGF, reduce the content of collagen and α-SMA in the intestinal wall of mice with chronic colitis, and inhibit the fibrosis of the intestinal wall.