p38丝裂原活化蛋白激酶对腹主动脉瘤组织基质金属蛋白酶表达的影响

Effects of p38 mitogen activated protein kinase on expression of matrix metalloproteinases in human tissue of abdominal aortic aneurysm

目的 观察腹主动脉瘤（AAA）组织内磷酸化丝裂原激活蛋白激酶p38 （p38MAPK）活性表达,及其对AAA局部组织基质金属蛋白酶（MMPs）等表达的影响.方法 AAA标本取自20例AAA患者术中切除的动脉瘤组织,10例正常腹主动脉标本取自尸体供肾者之修剪供肾时所得剪下弃用的腹主动脉壁.Western blot法检测瘤壁组织磷酸化p38MAPK活性,酶联免疫吸附试验（ELlSA）法检测培养上清液中MMP-2、MMP-9、肿瘤坏死因子-α（TNF-α）含量,在体外培养条件下,观察p38MAPK特异性阻滞剂SB203580对AAA组织中MMP-2、MMP-9、TNF-α表达的影响.结果 磷酸化p38MAPK吸光度（A）值在AAA组织（3.92±0.32）明显高于正常主动脉壁组织（1.19±0.037）;未经处理的AAA组织与经SB203580共培养处理过的AAA组织比较,培养上清液中TNF-α、MMP-9、MMP-2含量明显升高,浓度分别为（375.11±87.33）、（69.37±13.44） ng/L;（87.09±8.89）、（38.33 ±6.78） μg/L;（630.25±37.03）、（403.14±36.90） μg/L.结论 阻断p38MAPK转导通路,可减少AAA组织炎性反应及MMP-2、MMP-9的表达.

Objective To reaserch the relationship between the activity of p38 mitogen activated protein kinase （p38MAPK） and the expression of matrix metalloproteinases （MMPs） in tissue of abdominal aortic aneurysm （AAA）.Methods AAA specimens were taken from AAA tissues of 20 patients with AAA in surgical procedure of resection of the aneurysm,and 10 cases of normal abdominal aorta specimens were taken from abdominal aortic wall cut by cadaveric donor kidney.Western blotting was used to detect the activity of phosphorylated p38MAPK in AAA wall,and enzyme linked immunosorbent assay （ELISA） to determine the contents of MMP-2,MMP-9 and tumor necrosis factor-α （TNF-α） in the culture supernatant.The efffect of SB203580 on the expression of MMP-2,MMP-9 and TNF-α in AAA group was observed.Results As compared with the normal abdominal aortic wall,the activity of p38MAPK was significantly increased in AAA group （3.92 ± 0.32 vs.1.19 ± 0.037）;The levels of TNF-α,MMP-9 and MMP-2 in the supernatant were remarkablely increased in the untreated group [（375.11 ± 87.33） ng/L,（87.09 ± 8.89） μg/L,and （630.25 ± 37.03） μg/L] as compared with the group treated with SB203580 [（69.37 ± 13.44） ng/L,（38.33 ±6.78） μg/L,and （403.14 ±36.90） μg/L].Conclusion Blocking p38MAPK transduction pathway can reduce the inflammatory response and the expression of MMP-2 and MMP-9 in AAA groups.