本文選題：二甲基肼 + 環(huán)氧合酶-2�。� 參考：《遵義醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:探討環(huán)氧合酶-2(COX-2)、5-脂氧合酶(5-LOX)與大腸腺瘤發(fā)生、發(fā)展的關(guān)系及兩者之間是否存在動(dòng)態(tài)關(guān)系,為大腸腫瘤的靶向治療提供新的理論依據(jù)。方法:選用SD大鼠55只,隨機(jī)分為5組,其中干預(yù)組每組10只,分別為DMH+Celecoxib組、DMH+Zileuton組、DMH+Celecoxib+Zileuton組,DMH組15只,對(duì)照組10只。DMH+Celecoxib組每周予以二甲基肼(20mg/kg)腹腔注射,同時(shí)予COX-2抑制劑(Celecoxib 50mg/kg)灌胃,隔日1次;DMH+Zileuton組每周予以DMH(20mg/kg)腹腔注射,同時(shí)予5-LOX抑制劑(Zileuton 50mg/kg)灌胃,隔日1次;DMH+Celecoxib+Zileuton組每周予以二甲基肼(20mg/kg)腹腔注射,同時(shí)予COX-2抑制劑(Celecoxib 25mg/kg)+5-LOX抑制劑(Zileuton 25mg/kg)聯(lián)合灌胃,隔日1次;DMH組每周單純予以DMH(20mg/kg)腹腔,并予同等量生理鹽水灌胃;對(duì)照組每周腹腔注射等量生理鹽水,予同等量生理鹽水灌胃。分別第18周、20周、22周處死老鼠。HE染色了解模型構(gòu)建情況。酶聯(lián)免疫法檢測(cè)大腸組織中的PGE2和LTB4濃度,免疫組織化學(xué)法檢測(cè)大腸組織中的Ki-67表達(dá),實(shí)時(shí)定量PCR檢測(cè)大腸組織中的COX-2 m RNA、5-LOX m RNA表達(dá),并作分析。結(jié)果:(1)實(shí)驗(yàn)組及干預(yù)組大鼠大腸腫瘤成瘤率64.3%,對(duì)照組未見(jiàn)大腸腫瘤發(fā)生。(2)RT-PCR檢測(cè)的結(jié)果顯示,COX-2/5-LOX m RNA在各組中均有表達(dá),DMH組、DMH+Celecoxib組、DMH+Zileuton組、DMH+Celecoxib+Zileuton組COX-2/5-LOX m RNA的表達(dá)均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH組COX-2/5-LOX m RNA的表達(dá)高于DMH+Celecoxib組、DMH+Zileuton組及DMH+Celecoxib+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Zileuton組COX-2m RNA的表達(dá)高于DMH+Celecoxib組及DMH+Celecoxib+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Celecoxib+Zileuton組COX-2 m RNA的表達(dá)約高于DMH+Celecoxib組,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Celecoxib組5-LOX m RNA的表達(dá)高于DMH+Zileuton組及DMH+Celecoxib+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Zileuton組5-LOX m RNA的表達(dá)約高于DMH+Celecoxib+Zileuton組,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)ELISA法檢測(cè)PGE2/LTB4,結(jié)果顯示PGE2/LTB4在各組大腸組織中均有表達(dá),測(cè)不同組大腸組織中PGE2/LTB4的含量,且對(duì)其進(jìn)行比較,結(jié)果DMH+Celecoxib組、DMH+Zileuton組、DMH+Celecoxib+Zileuton組、DMH組PGE2/LTB4的含量均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH組PGE2/LTB4的含量高于DMH+Celecoxib組、DMH+Zileuton組、DMH+Celecoxib+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Zileuton組PGE2的含量高于DMH+Celecoxib組及DMH+Celecoxib+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Celecoxib組PGE2的含量約高于DMH+Celecoxib+Zileuton組,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);DMH+Celecoxib組LTB4的含量高于DMH+Zileuton組及DMH+Celecoxib+Zileuton組,差異具有統(tǒng)計(jì)學(xué)意義(P0.05),DMH+Zileuton組LTB4的含量約高于DMH+Celecoxib+Zileuton組,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)免疫組化法檢測(cè)Ki-67不同組大腸組織中的均有表達(dá),Ki-67在對(duì)照組、DMH+Celecoxib+Zileuton組、DMH+Celecoxib組、DMH+Zileuton組、DMH組的陽(yáng)性表達(dá)率分別為16.67%(2/12)、31.3%(5/16)、40.0%(6/15)、50.0%(9/18)、77.78%(35/45),DMH組高于DMH+Celecoxib+Zileuton組、DMH+Celecoxib組、DMH+Zileuton組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1.COX-2、5-LOX及其PEG2、LTB4在結(jié)直腸腺瘤-腺癌發(fā)生發(fā)展過(guò)程中表達(dá)逐漸增加。2.應(yīng)用COX-2/5-LOX抑制劑,可使COX-2/5-LOX m RNA及代謝產(chǎn)物PGE2/LTB4的減少,抑制結(jié)直腸細(xì)胞增殖,有抑制結(jié)直腸腺瘤-腺癌發(fā)生發(fā)展的趨勢(shì)。3.COX-2/5-LOX通路之間存在一定的協(xié)同性。
[Abstract]:Objective: To explore the relationship between the occurrence and development of -2 (COX-2), 5- lipoxygenase (5-LOX) and colorectal adenoma, and whether there is a dynamic relationship between them, and to provide a new theoretical basis for the target treatment of colorectal tumors. Methods: 55 rats of SD were selected and divided into 5 groups randomly, of which 10 rats in each group were group DMH+Celecoxib, DMH+Zileuton Group DMH+Celecoxib+Zileuton, group DMH+Celecoxib+Zileuton and group DMH, 10.DMH+Celecoxib groups in the control group were injected with two methyl hydrazine (20mg/kg) per week, and COX-2 inhibitor (Celecoxib 50mg/kg) was given to the stomach and 1 times a day; DMH+Zileuton group was given DMH (20mg/kg) intraperitoneal injection every week, and 5-LOX inhibitor (Zileuton) was given to the stomach and 1 times a day. Group oxib+Zileuton was intraperitoneally injected with two methylhydrazine (20mg/kg) per week, while the COX-2 inhibitor (Celecoxib 25mg/kg) +5-LOX inhibitor (Zileuton 25mg/kg) was administered to the stomach and 1 times a day. The DMH group was given the DMH (20mg/kg) abdominal cavity per week, and the same amount of normal saline was given to the stomach. The control group was intraperitoneally injected with equal amount of saline for the same amount of birth every week. Eighteenth weeks, 20 weeks, 22 weeks, eighteenth weeks, 20 weeks and 22 weeks, the rats were killed to understand the model construction. The enzyme linked immunosorbent assay was used to detect the concentration of PGE2 and LTB4 in the large intestine tissue, the immunohistochemical method was used to detect the expression of Ki-67 in the large intestine tissue. The real-time quantitative PCR was used to detect the COX-2 m RNA in the large intestine tissue and 5-LOX m RNA expression, and the results were analyzed. Results (1) real The rate of colorectal tumor formation was 64.3% in the test group and the intervention group, and there was no colorectal tumor in the control group. (2) the results of RT-PCR detection showed that COX-2/5-LOX m RNA was expressed in all groups. The expression of COX-2/5-LOX m RNA in group DMH, DMH+Celecoxib, DMH+Zileuton and DMH+Celecoxib+Zileuton group was higher than that of the control group, and the difference was statistically significant (P0.05). The expression of COX-2/5-LOX m RNA in group DMH was higher than that in group DMH+Celecoxib, DMH+Zileuton group and DMH+Celecoxib+Zileuton group, and the difference was statistically significant (P0.05). The expression of COX-2m RNA in group DMH+Zileuton was higher than that in DMH+Celecoxib group and group. The difference of 5-LOX m RNA in group DMH+Celecoxib was higher than that of group DMH+Zileuton and DMH+Celecoxib+Zileuton group, and the difference was statistically significant (P0.05). The expression of 5-LOX m in the DMH+Zileuton group was higher than that in the group of DMH+Zileuton (P0.05). There was no significant difference in the expression of 5-LOX m in the DMH+Zileuton group. (3) the 5-LOX m RNA was not statistically significant. B4, the results showed that PGE2/LTB4 was expressed in all groups of large intestine tissues, and the content of PGE2/LTB4 in different groups of large intestine tissues was measured and compared. The results showed that the content of PGE2/LTB4 in group DMH+Celecoxib, DMH+Zileuton, DMH+Celecoxib+Zileuton and DMH was higher than that of the control group, the difference was statistically significant (P0.05), and the PGE2/LTB4 content in DMH group was higher than that of the control group. The difference between group DMH+Celecoxib, group DMH+Zileuton and group DMH+Celecoxib+Zileuton was statistically significant (P0.05). The content of PGE2 in group DMH+Zileuton was higher than that in group DMH+Celecoxib and DMH+Celecoxib+Zileuton group, and the difference was statistically significant (P0.05). The PGE2 content of DMH+Celecoxib group was higher than that of DMH+Celecoxib+Zileuton group, and there was no statistical significance. The content of LTB4 in group MH+Celecoxib was higher than that of group DMH+Zileuton and DMH+Celecoxib+Zileuton group, the difference was statistically significant (P0.05), the content of LTB4 in group DMH+Zileuton was higher than that of DMH+Celecoxib+Zileuton group, and the difference was not statistically significant (P0.05). (3) immunohistochemistry was used to detect the expression of Ki-67 in different groups of large intestine tissues, Ki-67 in the control group, DMH+. The positive rates of Celecoxib+Zileuton, DMH+Celecoxib, DMH+Zileuton and DMH were 16.67% (2/12), 31.3% (5/16), 40% (6/15), 50% (9/18), 77.78% (35/45). The DMH group was higher than the DMH+Celecoxib+Zileuton group. During the development of adenoma and adenocarcinoma, the expression of the.2. COX-2/5-LOX inhibitor is gradually increased, which can reduce the COX-2/5-LOX m RNA and the metabolite PGE2/LTB4, inhibit the proliferation of colorectal cells, and inhibit the development of colorectal adenoma and adenocarcinoma, and there is a certain synergism between the.3.COX-2/5-LOX pathway.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.34

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9 陸啟瑜;丹參聯(lián)合Celecoxib治療對(duì)大鼠重癥急性胰腺炎肺損傷Cycloxygenase-2的相關(guān)機(jī)制研究[D];昆明醫(yī)學(xué)院;2009年

10 林奇;docetaxel抗血管生成化療與celecoxib聯(lián)合應(yīng)用抑制胃癌生長(zhǎng)及轉(zhuǎn)移的實(shí)驗(yàn)研究[D];蘇州大學(xué);2005年

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