| Object:The aim of our study was to investigate the effect of vitamin D in DSS-induced ulcerative colitis in C57BL/6 mice and elucidate the mechanisms of vitamin D in NF-κB pathway.Method:Thirty-six 6-week-old C57BL/6 female mice were randomly divided into four groups: normal group(Control), ulcerative colitis model group(Model), 50ng/kg·bw 1,25-(OH)2D3 group and 500ng/kg·bw 1,25-(OH)2D3 group. Colitis was induced by administering 5% DSS in the drinking water for 7 days.Distilled water was given to controls. 1,25-(OH)2D3 groups received the treatment daily by gastric lavage, while the other two groups received the same solvent. 9 days later, all the mice was killed. The serum, spleen and colon tissues were separated. The gross and histological score of colon and disease activity index were evaluated, measured colon length and the weight of spleen, calculation the organ index. The levels of TNF-α and IL-6 protein in serum were measured by ELISA, the protein expression of p- IKKβ, p-IκB, NF-κBp65 and Vitamin D Receptor in colonic tissues was measured by immunohistochemistry.Results:1. The colitis model was successfully established in mice given 5% DSS. The mice treated by DSS suffered from spiritual, dull hair, different degrees of weight loss, diarrhea and bloody stool from the third day. The mice treated by vitamin D were better than mice in model group(P<0.05).2. Compared with the control group, mice in the model group appeared body-weightloss, bloody stool and diarrhea, and had a higher DAI. Mice in the vitamin D treated group had a lower DAI than the model group. Mice in the model group had a higher DAI on the seventh day than the control group(P<0.05), mice in the 50ng/kg·bw 1,25-(OH)2D3 group had a lower DAI on the seventh day than the model group(P<0.05), mice in the 500ng/kg·bw 1,25-(OH)2D3 group had the lowest DAI on the seventh day in three DSS treated groups(P<0.05).3. Intestinal injury was lighter in the vitamin D treated group. Mice in the model group had a higher score in gross and histological rating of colon, mice in the 50ng/kg·bw 1,25-(OH)2D3 group had a lower gross and histological score than mice in the model group(P<0.05) and the 500ng/kg·bw 1,25-(OH)2D3 group’s score was the lowest in three DSS treated groups(P<0.05). The model group’s colon length was significantly lower than control group. The vitamin D group’s colon length was longer than model group.4. The spleen were affected in mice with ulcerative colitis and vitamin D can mitigate these. The weight of spleens of mice in model group were heavier and the organ indexes were higher than these in control group(P<0.05). Mice in the vitamin D treated group had lower weight and organ indexes(P<0.05).5. Compared with the control group, the expression of TNF-α and IL-6 protein in serum in model group mice were higher(P<0.05). Compared with the model group, 1,25-(OH)2D3 treated group had a decrease on the expression of TNF-α and IL-6 protein in serum(P<0.05).6. Compared with the control group, the expression of p- IKKβ(P<0.05), p-IκBα(P<0.05) and NF-κBp65(P<0.05) in colonic tissues in model group mice were higher. Compared with the model group, 1,25-(OH)2D3 treated group had a decrease on the expression of p- IKKβ(P<0.05), p-IκBα(P<0.05) and NF-κBp65(P<0.05) in colonic tissues.Conclusions:1. The colitis model was successfully established in mice given 5% DSS.2. Vitamin D can mitigated intestinal injury induced by DSS.3. Vitamin D can mitigate the injury in spleens in mice with ulcerative colitis.4. Vitamin D can inhibit inflammatory reaction by restraining the secretion of TNF-α and IL-6 protein in serum.5. Vitamin D has a suppression in NF-κB pathway by inhibiting IKK’s phosphorylation in colon tissues. The depressing of phosphorylated IKK lead to lower phosphorylation of IκB, and then inhibited the activated of NF-κB in colon tissues. |
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