發(fā)布時間：2018-04-25 18:49

  本文選題：食管癌 + 癌前病變　； 參考：《山東大學》2017年碩士論文

【摘要】：目的建立化學致癌劑4-硝基喹啉-1-氧化物(4NQO)誘導的KM小鼠食管癌前病變模型;通過HE染色和病理組織學檢測方法,觀察并分析沙棘干乳劑對食管癌前病變的阻斷作用。方法選取145只健康昆明小鼠,雌雄各半,隨機分為4組:A組(空白對照組)10只、B組(單純誘癌組)45只、C組(沙棘干乳劑治療組)45只、D組(全反式維甲酸陽性對照組)45只。(1)A組:實驗開始第1天～24周末,正常飲食、飲蒸餾水,不施加干預;B組:實驗開始第1天～14周,自由飲用濃度0.1g/mL的4NQO水溶液,第14周末將4NQO水溶液改為飲用蒸餾水;C組:實驗開始第1天～14周,自由飲用濃度O.1g/mL的4NQO水溶液,第14周末將4NQO水溶液改為飲用蒸餾水,并增加沙棘干乳劑(研究藥物)灌胃,持續(xù)至實驗結(jié)束;D組:實驗開始第1天～14周,自由飲用濃度0.1g/mL的4NQO水溶液,第14周末將4NQO水溶液改為飲用蒸餾水,并增加全反式維甲酸(陽性對照藥物)灌胃,持續(xù)至實驗結(jié)束。(2)實驗第10周末、第12周末、第14周末,均分別解剖A組小鼠2只、B組小鼠2只,于第14周末時,病理組織學檢測結(jié)果證實模型建立成功;第19周末時,分別解剖A組小鼠2只,B、C、D組各組20只;24周末時,解剖各組剩余小鼠。通過HE染色和病理組織學檢測方法縱向動態(tài)觀察4NQO誘導的小鼠食管上皮黏膜組織發(fā)生癌前病變的變化過程;同時橫向比較各組小鼠的食管上皮黏膜組織的增生程度,觀察并分析沙棘干乳劑對小鼠食管癌前病變的阻斷作用。結(jié)果(1)第14周末時:B組5例小鼠出現(xiàn)食管上皮黏膜組織輕度異型增生3例、中度異型增生1例、重度異型增生1例,異型增生率(輕+中+重度異型增生)為100%(5/5);(2)第19周末時:A、B、C、D四組同期相比,患癌率均無顯著性差異(fisher P=0.927);B、C、D三組同期相比,輕+中度異型增生率、重度異型增生+癌變率均無顯著性差異(χ~2=2.679,P0.05);(3)第24周末時:C組和B組同期相比,C組患癌率明顯低于B組(χ~2=6.561,P0.05);D組與B組同期相比,D組患癌率明顯低于B組(χ~2=10.506,P0.05);C組與D組同期相比,兩組患癌率無顯著性差異(χ~2=0.739,P0.05);結(jié)論(1)通過連續(xù)14周自由飲用濃度為0.1g/mL的4NQO水溶液的方法,可成功建立KM小鼠食管癌前病變模型;(2)沙棘干乳劑對食管癌前病變有一定的阻斷作用,從而可以減緩食管癌前病變發(fā)展的進程,防止進一步惡變;且其阻斷作用程度與全反式維甲酸相當。目的比較鈣離子激活氯離子通道蛋白1(anoctamin1,ANO1)、表皮生長因子受體(Epidermal Growth Factor Receptor,EGFR)蛋白在小鼠不同食管上皮組織病變中的表達,探討ANO1、EGFR蛋白表達與小鼠食管上皮黏膜組織病變的關系,為早期食管癌變診斷提供參考。方法應用化學致癌劑4硝基喹琳1氧化物(4NQO)由飲水法建立小鼠食管癌前病變模型,應用免疫組化方法檢測小鼠不同食管上皮病變中EGFR、ANO1蛋白的表達水平。結(jié)果(1)ANO1表達定位于細胞漿,其中正常組織、輕度異型增生組織、中度異型增生組織、重度異型增生組織和癌變組織中的ANO1蛋白陽性表達率分別為 0%(0/14)、0%(0/25)、2.56%(1/39)、34.78%(8/23)和 50.00%(22/44);ANO1在癌組織中的陽性率顯著高于正常組織(χ~2=11.278,P0.05)、輕度異型增生組織(χ~2=18.351,P0.05)及中度異型增生組織(χ~2=23.224,P0.05);ANO1在重度異型增生組織中的陽性率顯著高于正常組織(fisher P=0.015)、輕度異型增生組織(χ~2=8.081,P0.05)及中度異型增生組織(χ~2=9.645,P0.05)。(2)EGFR表達定位于細胞漿,其中正常組織、輕度異型增生組織、中度異型增生組織、重度異型增生組織和癌變組織中的EGFR蛋白陽性表達率分別為7.14%(1/14)、16.00%(4/25)、23.08%(9/39)、52.17%(12/23)和 59.09%(26/44);EGFR在癌組織中的陽性率顯著高于正常組織(χ~2=11.519,P0.05)、輕度異型增生組織(χ~2=12.046,P0.05)及中度異型增生組織(χ~2=10.996,P0.05);EGFR在重度異型增生組織中的陽性率顯著高于正常組織(fisher P=0.011)、輕度異型增生組織(X2=7.054,P0.05)及中度異型增生組織(χ~2=5.469,P0.05)。67例重度異型增生及癌變組織中,ANO1表達陽性組中EGFR陽性率為93.33%(28/30),ANO1 表達陰性組中 EGFR 陰性率為 72.97%(27/37),ANO1 和 EGFR的表達相關系數(shù)r=0.665,相關性具有顯著性意義(P0.05)。結(jié)論(1)ANO1在重度異型增生及癌變組織中表達特異性高,提示其參與食管癌的發(fā)生發(fā)展,并有可能成為新的食管癌藥物治療靶點和生物學標記;(2)ANO1、EGFR在食管重度異型增生及癌變組織中的表達呈一定正相關,兩者的雙向交互作用可能為其機制。
[Abstract]:Objective to establish a precancerous precancerous lesion model in KM mice induced by chemical carcinogen 4- nitroquinoline -1- oxide (4NQO), and to observe and analyze the blocking effect of seabuckthorn dry emulsion on precancerous lesions of the esophagus by HE staining and histopathological detection. Methods 145 healthy Kunming rats were selected and divided into 4 groups randomly: A group (blank control) Group B (group B) 45, group C (Seabuckthorn dry emulsion treatment group) 45, group D (all trans retinoic acid positive control group) 45. (1) group A: the experiment began first days to 24 weekend, normal diet, drink distilled water, no intervention; B group: the experiment began first to 14 weeks, free drinking concentration of 0.1g/mL 4NQO solution, fourteenth weekend 4NQO water solution, fourteenth weekend solution 4NQO water solution. The liquid was changed to distilled water for drinking. Group C: the experiment started first to 14 weeks, the free drinking concentration of 4NQO solution of O.1g/mL was free, the 4NQO solution was changed into drinking distilled water at the end of the fourteenth week, and the Seabuckthorn dry emulsion was added to the stomach and continued to the end of the experiment; group D: the experiment began first to 14 weeks, the free drinking concentration of 0.1g/mL 4NQO solution, fourteenth weeks At the end, the 4NQO water solution was changed into drinking distilled water, and all trans retinoic acid (positive control drugs) was added to the stomach and continued to the end of the experiment. (2) 2 mice in group A and 2 mice in group B were dissected respectively at the weekend of the experiment, twelfth weekend and fourteenth weekend. At the end of the fourteenth week, the pathological histological examination confirmed the success of the model; nineteenth weekend, respectively, respectively. 2 mice in group A, 20 rats in group B, C and D were dissected. At the 24 weekend, the remaining mice were dissected. The changes in the precancerous lesion of the esophageal epithelium induced by 4NQO were observed longitudinally by HE staining and histopathological detection, and the degree of proliferation of esophageal epithelial tissue in each group was compared and observed and observed. The blocking effect of seabuckthorn dry emulsion on precancerous lesions of the esophagus in mice was analyzed. Results (1) at the end of fourteenth weeks, 5 mice in group B showed mild dysplasia in esophageal epithelium, 1 cases of moderate dysplasia, 1 severe dysplasia, 100% (5/5) with the rate of dysplasia (mild + severe atypical growth), and (2) nineteenth weekend: A, B, C, and D four group of four phase There was no significant difference in the rate of cancer (Fisher P=0.927), and there was no significant difference in the rate of light + moderate dysplasia, severe dysplasia and cancer (P0.05) in the three groups of B, C and D. (3) at the twenty-fourth weekend, the cancer rate in the C and B groups was significantly lower than that in the B group (x ~2=6.561,). Compared with group B (x ~2=10.506, P0.05), there was no significant difference between the two groups in the C group and the D group (x ~2=0.739, P0.05), and (1) the esophageal precancerous lesion model of KM mice could be successfully established by the method of 4NQO aqueous solution of 0.1g/mL for 14 weeks of free drinking, and (2) the Seabuckthorn dry emulsion had a certain blocking effect on the precancerous lesions of the esophagus. It can be used to slow down the progression of precancerous lesions of the esophagus and prevent further malignant change; and its blocking effect is equivalent to all trans retinoic acid. Objective to compare calcium ion activated chloride channel protein 1 (anoctamin1, ANO1), Epidermal Growth Factor Receptor, EGFR protein in different esophageal epithelial tissues in mice The relationship between the expression of ANO1, EGFR protein and the pathological changes of esophageal epithelial mucosa in mice was discussed in order to provide reference for the diagnosis of early esophageal carcinogenesis. Methods the chemical carcinogen 4 nitroquinine 1 oxide (4NQO) was used to establish the precancerous precancerous lesion model of mice by drinking water method, and the different esophageal epithelial diseases in mice should be detected by immunohistochemical method. The expression level of EGFR, ANO1 protein. Results (1) the expression of ANO1 was located in the cytoplasm. The positive expression rates of ANO1 protein in normal tissue, mild dysplasia, severe dysplasia, severe dysplasia and cancerous tissues were 0% (0/14), 0% (0/25), 2.56% (1/39), 34.78% (8/23) and 50% (22/44); ANO1 in the cancer group. The positive rate in the fabric was significantly higher than that of normal tissue (x ~2=11.278, P0.05), mild dysplasia (x ~2=18.351, P0.05) and moderate dysplasia (x ~2=23.224, P0.05). The positive rate of ANO1 in severe dysplasia was significantly higher than that of normal tissue (Fisher P =0.015), and the mild dysplasia (chi ~2=8.081, P0.05) and moderate atypia were increased. (x ~2=9.645, P0.05). (2) the expression of EGFR was located in the cytoplasm. The positive rates of EGFR protein expression in normal tissue, mild dysplasia, severe dysplasia, severe dysplasia and cancerous tissues were 7.14% (1/14), 16% (4/ 25), 23.08% (9/39), 52.17% (12/23) and 59.09% (26/44); EGFR was in the cancer tissue. The positive rate was significantly higher than that of normal tissue (x ~2=11.519, P0.05), mild dysplasia (x ~2=12.046, P0.05) and moderate dysplasia (x ~2=10.996, P0.05). The positive rate of EGFR in severe dysplasia was significantly higher than that of normal tissue (Fisher P=0.011), mild dysplasia (X2=7.054, P0.05) and moderate dysplasia (P0.05). The positive rate of EGFR in ANO1 expression positive group was 93.33% (28/30), EGFR negative rate in ANO1 negative group was 72.97% (27/37) in ANO1 negative group, and the correlation coefficient of ANO1 and EGFR was significant (1) in severe dysplasia and cancerous tissue in.67 negative group.67. It has high expression specificity, suggesting that it participates in the development of esophageal cancer and may become a new target for the treatment of esophageal cancer and biological markers. (2) ANO1, EGFR is positively correlated with the expression of severe dysplasia and cancerous tissues of the esophagus, and the two-way interaction between them may be the mechanism.

【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.1

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