环氧合酶-2、5-脂氧合酶与大肠腺瘤发生、发展的关系
本文选题：二甲基肼 + 环氧合酶-2 ； 参考：《遵义医学院》2017年硕士论文
【摘要】：目的:探讨环氧合酶-2(COX-2)、5-脂氧合酶(5-LOX)与大肠腺瘤发生、发展的关系及两者之间是否存在动态关系,为大肠肿瘤的靶向治疗提供新的理论依据。方法:选用SD大鼠55只,随机分为5组,其中干预组每组10只,分别为DMH+Celecoxib组、DMH+Zileuton组、DMH+Celecoxib+Zileuton组,DMH组15只,对照组10只。DMH+Celecoxib组每周予以二甲基肼(20mg/kg)腹腔注射,同时予COX-2抑制剂(Celecoxib 50mg/kg)灌胃,隔日1次;DMH+Zileuton组每周予以DMH(20mg/kg)腹腔注射,同时予5-LOX抑制剂(Zileuton 50mg/kg)灌胃,隔日1次;DMH+Celecoxib+Zileuton组每周予以二甲基肼(20mg/kg)腹腔注射,同时予COX-2抑制剂(Celecoxib 25mg/kg)+5-LOX抑制剂(Zileuton 25mg/kg)联合灌胃,隔日1次;DMH组每周单纯予以DMH(20mg/kg)腹腔,并予同等量生理盐水灌胃;对照组每周腹腔注射等量生理盐水,予同等量生理盐水灌胃。分别第18周、20周、22周处死老鼠。HE染色了解模型构建情况。酶联免疫法检测大肠组织中的PGE2和LTB4浓度,免疫组织化学法检测大肠组织中的Ki-67表达,实时定量PCR检测大肠组织中的COX-2 m RNA、5-LOX m RNA表达,并作分析。结果:(1)实验组及干预组大鼠大肠肿瘤成瘤率64.3%,对照组未见大肠肿瘤发生。(2)RT-PCR检测的结果显示,COX-2/5-LOX m RNA在各组中均有表达,DMH组、DMH+Celecoxib组、DMH+Zileuton组、DMH+Celecoxib+Zileuton组COX-2/5-LOX m RNA的表达均高于对照组,差异有统计学意义(P0.05),DMH组COX-2/5-LOX m RNA的表达高于DMH+Celecoxib组、DMH+Zileuton组及DMH+Celecoxib+Zileuton组,差异有统计学意义(P0.05),DMH+Zileuton组COX-2m RNA的表达高于DMH+Celecoxib组及DMH+Celecoxib+Zileuton组,差异有统计学意义(P0.05),DMH+Celecoxib+Zileuton组COX-2 m RNA的表达约高于DMH+Celecoxib组,差异无统计学意义(P0.05),DMH+Celecoxib组5-LOX m RNA的表达高于DMH+Zileuton组及DMH+Celecoxib+Zileuton组,差异有统计学意义(P0.05),DMH+Zileuton组5-LOX m RNA的表达约高于DMH+Celecoxib+Zileuton组,差异无统计学意义(P0.05)。(3)ELISA法检测PGE2/LTB4,结果显示PGE2/LTB4在各组大肠组织中均有表达,测不同组大肠组织中PGE2/LTB4的含量,且对其进行比较,结果DMH+Celecoxib组、DMH+Zileuton组、DMH+Celecoxib+Zileuton组、DMH组PGE2/LTB4的含量均高于对照组,差异有统计学意义(P0.05),DMH组PGE2/LTB4的含量高于DMH+Celecoxib组、DMH+Zileuton组、DMH+Celecoxib+Zileuton组,差异有统计学意义(P0.05),DMH+Zileuton组PGE2的含量高于DMH+Celecoxib组及DMH+Celecoxib+Zileuton组,差异有统计学意义(P0.05),DMH+Celecoxib组PGE2的含量约高于DMH+Celecoxib+Zileuton组,差异无统计学意义(P0.05);DMH+Celecoxib组LTB4的含量高于DMH+Zileuton组及DMH+Celecoxib+Zileuton组,差异具有统计学意义(P0.05),DMH+Zileuton组LTB4的含量约高于DMH+Celecoxib+Zileuton组,差异无统计学意义(P0.05)。(3)免疫组化法检测Ki-67不同组大肠组织中的均有表达,Ki-67在对照组、DMH+Celecoxib+Zileuton组、DMH+Celecoxib组、DMH+Zileuton组、DMH组的阳性表达率分别为16.67%(2/12)、31.3%(5/16)、40.0%(6/15)、50.0%(9/18)、77.78%(35/45),DMH组高于DMH+Celecoxib+Zileuton组、DMH+Celecoxib组、DMH+Zileuton组,差异有统计学意义(P0.05)。结论:1.COX-2、5-LOX及其PEG2、LTB4在结直肠腺瘤-腺癌发生发展过程中表达逐渐增加。2.应用COX-2/5-LOX抑制剂,可使COX-2/5-LOX m RNA及代谢产物PGE2/LTB4的减少,抑制结直肠细胞增殖,有抑制结直肠腺瘤-腺癌发生发展的趋势。3.COX-2/5-LOX通路之间存在一定的协同性。
[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.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34
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