Establishment and evaluation of colon inflammation-tumor transformation model in Wistar rats induced by DSS/DMH combination
Objective:Based on the combination of dextran sodium sulfate(DSS)/dimethyl hydrazine(DMH),the inflammation-tumor transformation model of colon in Wistar rats was established and evaluated.Methods:Forty Wistar rats were given 4％DSS at a dose of 30 mL/d for 3 days to establish UC inflammatory phase model.Thirty-four UC rat models in the UC inflammatory phase were randomly selected and continued to be given DSS until the 7th day(8 of them died)to establish UC active phase models.Twenty UC active phase rat models were randomly selected,and injected with DMH at a dose of 25 mg/kg per week for 17 weeks(4 of them died)to establish the UC-CAC transformation phase model.Ten UC-CAC transformation phase rat model rats were randomly selected and treated with DMH until 24 weeks(4 of them died)to establish CAC phase model.A normal group and a PBS control group were set and with 6 rats in each group.The characteristics of rats and tumors in different phases of colon inflammation-tumor transformation were observed.Colon length,wall thickness and wet mass index were measured,and DAI and CMDI scores were evaluated.The levels of C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and hemoglobin(HGB)were detected at each phase.The pathological changes of colon were observed by Masson staining.The protein expressions of MLH1,PMS2,MSH2 and MSH6 were detected by immunohistochemistry.Results:The rats in UC inflammatory phase showed loose bloody stool,and diarrhea and blood stool in UC active phase became frequent.diarrhea and bloody stool aggravated in UC active phase;The tumorigenic rate of colon in rats during UC-CAC transformation phase was 66.67％(4/6),while 100.00％(6/6)in CAC phase;The body weight of CAC rats entered the compensatory period at 11 th-18th week,and then entered the decompensation phase;The colon length showed the lowest and the wet mass index and wall thickness demonstrated the highest in the CAC phase among the groups;The DAI and CMDI scores showed the highest in UC active phase and CAC phase respectively.The CRP level demonstrated highest in the UC active phase,and ESR and HGB reached the highest and lowest respectively in the CAC phase;Distortion and deformation of colonic crypt could be seen in the UC inflammatory phase,abscess ulceration in the UC active phase,and tubular moderately well-differentiated adenoma in the UC-CAC transformation phase.The CAC phase showed well-differentiated serrated adenoma;MLH1,PMS2,MSH2 and MSH6 proteins were negative in all cases.Conclusion:DSS/DMH combination could successfully establish colon inflammation-tumor transformation mode including UC inflammatory phase,UC active phase,UC-CAC transformation phase and CAC phase.The method is reliable and specific,which is consistent with the traditional Chinese medicine pathogenesis of dampness,heat,blood stasis and toxin developing into cancer.
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