腹主动脉瘤组织原纤维蛋白-1表达水平及其对患者生存结局的影响

Expression level of FBN1 in abdominal aortic aneurysm and its effect on survival outcome of patients

目的探讨腹主动脉瘤组织原纤维蛋白-1(FBN1)表达水平及其对患者生存结局的影响。方法收集45例腹主动脉瘤(AAA)患者主动脉瘤组织和29例正常腹动脉血管壁组织,免疫组织化学染色检测组织基质金属蛋白酶(MMP9)、FBN1蛋白表达定位,蛋白质免疫印迹法检测组织FBN1、MMP9蛋白表达水平,实时荧光定量PCR检测组织FBN1、MMP9 mRNA表达水平。对45例AAA患者进行随访,分析FBN1表达与患者病理资料及生存结局的关系。结果 FBN1、MMP9主要表达于动脉瘤组织巨噬细胞或平滑肌细胞,主动脉瘤组织FBN1、MMP9蛋白阳性表达率86.7%、93.3%均高于正常动脉壁组织34.5%、48.3%(χ~2=21.467,19.450,P<0.001)。主动脉瘤组织FBN1、MMP9 mRNA相对表达量分别为(1.89±0.19)和(2.29±0.31),正常动脉壁组织分别为(0.79±0.15)和(1.32±0.12),主动脉瘤组织FBN1、MMP9 mRNA相对表达量高于正常动脉壁组织(t=26.317,t=16.061,P<0.001),差异有统计学意义;主动脉瘤组织FBN1、MMP9蛋白表达量分别为(1.08±0.11)和(1.02±0.10),正常动脉壁组织分别为(0.29±0.06)和(0.39±0.07),主动脉瘤组织FBN1、MMP9蛋白表达量高于正常动脉壁组织(t=35.376,t=19.548,P<0.001)。对照组FBN1与MMP9表达无相关性(P>0.05),AAA组FBN1与MMP9表达呈成正相关(r=0.861,P<0.05),差异有统计学意义。主动脉瘤破裂及瘤体直径>8.0 cm患者FBN1表达水平高于瘤体直径≤8.0 cm者,差异有统计学意义(P=0.047)。FBN1阴性患者5年生存率为87.2%,FBN1阳性患者5年生存率为48.1%,FBN1阴性组5年生存率高于阳性组(χ~2=17.081,P<0.05)。结论腹主动脉瘤组织FBN1表达显著升高,FBN1表达越高,患者生存率越低,FBN1可以作为AAA患者生存结局的评估指标之一。

Objective To explore the expression level of fibrillin-1(FBN1)in abdominal aortic aneurysm and its effect on survival outcome of patients.Methods A total of 45 abdominal aortic aneurysm(AAA)patients′aortic aneurysm and 29 normal abdominal artery vessel wall tissue were collected.The expression level and localization of matrix metalloproteinases-9(MMP9)and FBN1 protein were detected by immunohistochemical staining,the MMP9 and FBN1 protein expression levels were detected by Western blotting,and the FBN1 and MMP9 mRNA expression levels were detected by real-time fluorescence quantitative PCR.Forty-five cases of AAA patients were followed up.The relationship between FBN1 expression and pathological data,survival outcome were analyzed.Results MMP9 and FBN1 were mostly expressed in the macrophages or smooth muscle cells,and the positive expression rates of MMP9 and FBN1 in aortic aneurysm tissues were significantly higher than those in normal arterial wall tissues[(86.7%vs 34.8%),(93.3%vs 48.3%),respectively](χ2=21.467,19.450,P<0.001).FBN1,MMP9 mRNA relative expressions in aortic tumor tissue were(1.89±0.19),(2.29±0.31),respectively,while those in normal arterial wall tissue were(0.79±0.15),(1.32±0.12),respectively.FBN1,MMP9 mRNA relative expressions in aortic aneurysm were significantly higher than those in the normal arterial wall tissue(t=26.317,t=16.061,P<0.001).FBN1,MMP9 protein expression levels in aortic aneurysm tissues were(1.0±0.11),(1.02±0.10),respectively,while those in normal arterial wall tissue were(0.29±0.06),(0.39±0.07),respectively.FBN1,MMP9 protein expression levels in aortic aneurysm were significantly higher than those in the normal arterial wall tissue(t=35.376,t=19.548,P<0.001).There was no correlation between the expressions of FBN1 and MMP9 in the control group(P>0.05),and the expression of FBN1 was significantly positively correlated with the expression of MMP9 in the AAA group(r=0.861,P<0.05).FBN1 expression level in patients with aortic aneurysm rupture and tumor diameter>8.0 cm was significantly higher than that in patients with tumor diameter≤8.0 cm(P=0.047).The 5 year survival rate of FBN1 negative patients was 87.2%,the 5-year survival rate of FBN1 negative group was 48.1%,the 5 year survival rate of FBN1 negative group was significantly higher than that of the positive group(χ2=17.081,P<0.05).Conclusions The expression of FBN1 in abdominal aortic aneurysm is significantly increased.The higherFBN1 expression,the lower the survival rate.FBN1 can be used as one of the evaluation indicators of AAA patients′survival outcome.