The Effect And Mechanism Of Lafutidine Combined With Mesalazine On DSS-Induced Colitis In Mice

Objective To investigate the effect and mechanism of lafutidine combined with mesalazine on DSS-induced in mice.Methods Fifty BALB/c female mice(6-8 weeks,18-22 g)were randomly divided into 5groups: normal control group(A),model group(B),lafutidine group(C,48 mg/kg /d),mesalazine group(D,50 mg/kg/d),and lafutidine combined with mesalazine group(E,lafutidine 48 mg/kg/d and mesalazine 50 mg/kg/d).Mice in group A mice were fed with distilled water,while mice in other groups were fed with 4% DSS for 7 consecutive days to establish an acute colitis mice model.All mice except in group A and B were simultaneously treated with 0.2 mLby gavage at prescribed doses twice a day for 7 consecutive days.The stool traits,body weight,and occult blood condition of mice were recorded to calculate DAI.All mice were sacrificed with ether anesthesia on the 8th day.Intestinal tissue damage was observed and recorded,and intestinal tissues and the spleen were removed and collected for subsequent analyses.The expressions of IL-8,IL-6 and TNF-? in intestinal tissues were detected by ELISA,and expressions of NF-?B p65 and iNOS were detected by Western blot and immunohistochemistry;.Results(1)The mice fed with DSS solution showed different degrees of loose stools,bloody stools,and weight loss.Compared with the normal group(group A),the lafutidine(group C)significantly alleviated the above symptoms,and the DAI score was also decreased(p <0.05).(2)Compared with the model group(group A),the expressions of IL-6(DSS vs lafutidine: 2088.15±129.74 vs 1377.04±111.85),IL-8(DSS vs lafutidine: 1582.22±279.18 vs868.33 ± 122.76),and TNF-?(DSS vs lafutidine: 2418.15 ± 423.15 vs 1699.63 ± 87.19)in intestinal tissues were significantly decreased(p<0.05)in the lafutidine group(group C).The expressions were further decreased(p<0.01)when mice were treated with both lafutidine and mesalazine(group E).(3)Compared with the model group(group A),the lafutidine(group C)significantly reduced the expressions of NF-? B p65 and iNOS in mice with DSS-induced colitis.The reduction was more significant(p<0.01)in mice treated with both lafutidine and mesalazine(group E).Conclusion(1)Lafutidine can reduce the inflammation in mice with DSS-induced colitis,and the effect achieved by down-regulating the expression of NF-?B p65 to reduce the activation of iNOS and to inhibit the inflammatory cytokine release,and it is significantly stronger combined with mesalazine.(2)Combined use of Lafutidine and mesalazine may be a new choice for clinical treatment of ulcerative colitis.