骨桥蛋白及NF-κB的表达与大鼠腹主动脉瘤发生的相关性

发布时间：2018-01-11 22:11

本文关键词：骨桥蛋白及NF-κB的表达与大鼠腹主动脉瘤发生的相关性　出处：《华中科技大学》2012年硕士论文　论文类型：学位论文

更多相关文章： 腹主动脉瘤 大鼠 骨桥蛋白 NF-κB MMP-2

【摘要】：目的构建大鼠腹主动脉瘤模型并观察大鼠腹主动脉瘤中骨桥蛋白（OPN）、核因子-κB（NF-κB）及基质金属蛋白酶-2（MMP-2）的表达情况，从而探讨大鼠腹主动脉瘤发生的分子机制。方法酶灌注法构建大鼠腹主动脉瘤模型,首次手术中测量大鼠腹主动脉直径，，术后2周再次手术，测量腹主动脉直径、取材；HE染色法检测腹主动脉的结构改变及炎性细胞浸润情况；特殊染色法检测腹主动脉中层弹力蛋白变化情况；免疫组化技术、WesternBlot法检测各组腹主动脉组织中OPN、NF-κB及基质金属蛋白酶-2（MMP-2）的表达量。结果成功构建大鼠腹主动脉瘤模型；腹主动脉瘤组术后直径扩张率（220.3%）明显高于对照组（112.3%）；HE染色结果显示腹主动脉瘤组动脉壁中各层结构紊乱，炎性细胞浸润程度显著增高；维多利亚特殊染色显示腹主动脉瘤组动脉壁有不同程度的弹力纤维消失，萎缩胶原纤维量大量增加；免疫组化结果显示OPN在腹主动脉瘤组、对照组及正常组动脉壁中的表达分别为7.5×1012±2.92×1011、3.07×10~5±2.58×10~5、0（F=6.59，P=0.004）；NF-κB在腹主动脉瘤组、对照组及正常组动脉壁中表达量分别为2.36×10~(10)±2.80×10~(10)、0、0（F=6.96，P=0.004）；MMP-2在腹主动脉瘤组、对照组及正常组动脉壁中的表达量分别是4.52×10~(10)±1.73×10~(10)、0、0（F=6.83，P=0.003）；WesternBlot结果显示OPN在腹主动脉瘤组、对照组及正常组动脉壁中的表达分别为2.77×10~5±2.82×10~5、4.52×10~3±1.36×10~3、2.11×10~3±1.99×10~3（F=9.49，P=0.001）；NF-κB在腹主动脉瘤组、对照组及正常组动脉壁中表达量分别为6.014×10~4±6.27×10~4、1.34×10~3±1.89×10~3、4.35×10~2±7.01×10~2（F=8.91，P=0.001）；MMP-2在腹主动脉瘤组、对照组及正常组动脉壁中的表达量分别是9.25×10~4±6.87×10~4、8.00×10~2±7.89×10~2、2.70×10~2±3.89×10~2（F=17.91，P㩳0.001），OPN、NF-κB及基质金属蛋白酶-2（MMP-2）呈正相关。结论成功构建大鼠腹主动脉瘤模型，骨桥蛋白、NF-κB及MMP-2与大鼠腹主动脉瘤形成存在相关性，骨桥蛋白可能通过NF-κB途径上调MMP的表达,过度表达的MMP加速了动脉壁中细胞外基质的降解而在大鼠腹主动脉瘤的发生发展中起到重要作用。
[Abstract]:Objective to establish a rat model of abdominal aortic aneurysm and to observe the expression of osteopontin (OPN), nuclear factor- 魏 B (NF- 魏 B) and matrix metalloproteinase-2 (MMP-2) in abdominal aortic aneurysm. To explore the molecular mechanism of abdominal aortic aneurysm in rats. Methods A rat model of abdominal aortic aneurysm was established by enzyme perfusion. The diameter of abdominal aorta was measured in the first operation. The changes of abdominal aorta structure and inflammatory cell infiltration were detected by HE staining. The changes of elastin in abdominal aorta were detected by special staining method. The expression of OPN- 魏 B and matrix metalloproteinase-2 (MMP-2) in abdominal aorta was detected by Western blot. Results A rat model of abdominal aortic aneurysm was successfully established. The diameter expansion rate of abdominal aortic aneurysm group (220.3%) was significantly higher than that of control group (112.3%). The results of HE staining showed that in the abdominal aortic aneurysm group, the structure of each layer was disordered, and the degree of inflammatory cell infiltration was significantly increased. Victorian special staining showed that elastic fibers disappeared and the amount of atrophy collagen fibers increased significantly in abdominal aortic aneurysm group. Immunohistochemical results showed that the expression of OPN was 7.5 脳 1012 卤2.92 脳 1011 in abdominal aortic aneurysm group, control group and normal group, respectively. 3.07 脳 10 ~ (5) 卤2.58 脳 10 ~ (5) F ~ (6. 59) P ~ (2 +) ~ (0.004); The expression of NF- 魏 B in abdominal aortic aneurysm group, control group and normal group were 2.36 脳 10 ~ (10)) 卤2.80 脳 10 ~ (10) ~ (10) ~ (10) ~ (10) F ~ (6) 6. 96 respectively. P0. 004; The expression of MMP-2 in abdominal aortic aneurysm group, control group and normal group were 4.52 脳 10 ~ (10) 卤1.73 脳 10 ~ (10) ~ (10) ~ (10) ~ (10) F ~ (6) 3 respectively. P0. 003; WesternBlot results showed that the expression of OPN was 2.77 脳 10 ~ 5 卤2.82 脳 10 ~ 5 in abdominal aortic aneurysm group, control group and normal group, respectively. 4.52 脳 10 ~ (3) 卤1.36 脳 10 ~ (3) C 2.11 脳 10 ~ (3) 卤1.99 脳 10 ~ (3) F ~ (9.49) C ~ (-1); The expression of NF- 魏 B was 6.014 脳 10 ~ 4 卤6.27 脳 10 ~ 4 in abdominal aortic aneurysm group, control group and normal group, respectively. 1.34 脳 10 ~ (3) 卤1.89 脳 10 ~ (3) C 4.35 脳 10 ~ (-2) 卤7.01 脳 10 ~ (2) F ~ (8.91) F ~ (2 +) ~ (0.001); The expression of MMP-2 in abdominal aortic aneurysm group, control group and normal group were 9.25 脳 10 ~ (4) 卤6.87 脳 10 ~ (4). 8.00 脳 10 ~ (2) 卤7.89 脳 10 ~ (2) C ~ (2.70 脳 10 ~ (2)) 卤3.89 脳 10 ~ (2) F ~ (17. 91)? There was a positive correlation between NF- 魏 B and matrix metalloproteinase-2 (MMP-2). Conclusion A rat model of abdominal aortic aneurysm was successfully established. Osteopontin NF- 魏 B and MMP-2 were correlated with the formation of abdominal aortic aneurysm in rats. Osteopontin may up-regulate the expression of MMP through NF- 魏 B pathway. Overexpression of MMP accelerates the degradation of extracellular matrix in arterial wall and plays an important role in the development of abdominal aortic aneurysm in rats.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R-332;R735.5

【参考文献】