| In order to study the regularity of clinical symptoms, colonic and extraintestinal manifestations, and changes in population, structure and function of intestinal paneth cells during UC induction phase, the experiments in this paper consisted of four parts by taking mouse model of acute colitis induced by 7%DSS as the research object. (1)Routine paraffin section and H&E staining were applied to study dynamic histopathologic changes in colon, liver, kidneys, spleen and lungs. (2) The clinical symptoms and colonic damages were analyzed and scored according to DAI and HI standard. (3) Paneth cells in small bowel and colon were studied by H&E staining and immunohistochemistry (mouseα-defensin-4 antibody used as primary antibody). (4) Applying acetic acid extraction and agarose diffusion methods, the antibacterial activity ofα-defensin in small bowel and colon extraction was detected by inhibition zone.The conclusions and results were shown four parts as follow.(1) BALB/c mice treated with 7days of 7% DSS developed acute colitis and resembled the features of human UC. The clinical condition and colon dynamic changes in this mice model performed obvious acute and severe character. The mice appeared several symptoms such as loose stools, occult blood and weight descents since day3. The colonic mucosa appeared erosion and hemorrhage, and the most severity occur in distal colon. DAI and HI score increased by gradually and were significantly different between day 1~7. On day 5 and 7, the colon were seriously damaged and mainly presented as crypt distortion, confluence even loss, and degeneration and necrosis of mucosal epithelial cells, accompanying with inequality of eosinophil infiltration. The crypt change preceded the damage of the epithelial cell and inflammation. The relationship between the crypt lesions and DAI correlated well in day3 and 5.(2) With UC developing, mice model in this experiment had several extraintestinal manifestations similar to human UC during induction phase, which was dominated by liver and kidney. On day 7, there were the most severe manifestations including multiple and local necrotic foci mainly distributed in liver middle lobe, and extensive swelled and complicated local hemorrhage and congestion in kidney. On day 1 and 3, no obvious extraintestinal lesion was observed. However since day 5, mice model behaved several extraintestinal histopathologic changes markedly, which mainly included that granular degeneration and vacuolation of hepatocytes; destructure and proliferation of the epithelial cells of interlobular bile duct; hemorrhage and congestion in sinusoid and renal interstitial. There was congestion in alveolar wall and inflammation at pulmonary bronchioles.(3) Treatment of 7% DSS had no obvious impact on paneth cell in small bowel and exclusively paneth cells proliferation in colon was characterized by expression ofα-defensin-4 and lack of acidophil granules. The population of paneth cells in duodenum, jejunum and ileum increased in succession and none was in colon. There was no significant difference between distinct induced time in small bowel(P>0.05). The results shown there were no significant difference inα-defensin-4 expression area ratio of jejunum and ileum between distinct induction time (P>0.05). Expression deletion in duodenum and colon on day 1, 3 and 5. Howeverα-defensin-4 expression was detected in colon on day 7, which located in hyperplasia crypt with eosinophile and neutrophil infiltration.(4) Exposure to 7% DSS had no marked effect onα-defensin in small bowel and no activeα-defensin was expressed in colon. The activity of extraction from ileum, jejunum and duodenum decreased in succession, but there was no difference between different time in the same segment (P>0.05). No inhibition activity was determined on day 1, 3, 5 and 7 in colon extraction.All the assays indicated UC mice model were developed by 7d administration of 7%DSS and had advantages of low mortality, good reproducibility, simple operation and prominent colonic symptoms. So this model may be beneficial to further research the mechanism of DSS induction, and offer integrated insights to UC model and administration time reference for various medication experiments. On day 7, metaplastic paneth cells occurred in colon and expressed no activeα-defensin, which demonstrated abnormal expression of paneth cells andα-defensin associated with the mechanism of UC. In addition, mice model processed apparent extraintestinal manifestations and paneth cells metaplasia. Therefore, it also could be applied to study on efficacy comparison and specific drug.
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