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1、温州医学院硕士学位论文MMP12血清水平及其基因82 AG多态性与颈动脉斑块稳定性的关系中文摘要 研究背景：流行病学研究说明，我国每年新发卒中病例约150200万例，校正年龄后的 每年脑卒中发病率为(116219)10万人口，年脑卒中死亡率为(58142)10 万人口【。目前现存脑血管病患者700余万人，其中约70为缺血性脑卒中。且 随着生活水平的提高，缺血性卒中越来越年轻化，近期国外统计了青年卒中发病 率竟高达(34113)10万人口【21，其不良预后不仅威胁着患者本人的生命和生 活，更给家庭乃至整个社会带来沉重的经济和心理负担。越来越多的证据说明， 颈动脉粥样硬化与缺血性卒中的发生、复发有
2、着密切的关系。随着对动脉粥样硬 化(Atherosclerosis，AS)研究的深入发现，大多数引起缺血性事件的病变不是位 于血管的最狭窄处，而是因为动脉粥样斑块破裂或裂隙伴随血栓形成造成的血管 堵塞所致【31。因此，影响颈动脉斑块稳定性的相关因素研究已成为缺血性脑卒中 领域关注的焦点。基质金属蛋白酶(Marix metalloproteinases，MMPs)是在细胞外基质 (Extracellular matrix，ECM)降解中起主要作用的锌离子依赖性蛋白酶超家族， 国内外大量的研究发现MMPs参与动脉粥样硬化的病理生理形成过程【4引。 MMP12(Marix metalloprotei
3、nase12)又被称为人巨噬细胞弹性蛋白酶，是MMPs家族中重要成员之一，可降解弹性蛋白酶、IV行胶原、纤维结合蛋白、层黏连 蛋白、玻璃粘连蛋白、蛋白聚糖、硫酸软骨素及髓鞘碱性蛋白。多项研究说明， MMP12可促进动脉粥样硬化的进展【617】。因此，研究血清MMP12水平与颈动 脉斑块稳定性之间的关系具有重要的意义。MMP12表达的调控主要发生在转录水平，研究发现MMP一12基因启动子 区82AG多态性可影响启动子的转录活性。既往研究发现MMP1282AG多态 性表达的增加与糖尿病患者冠状动脉狭窄增加密切相关【8】。目前，MMP一1282AG多态性与颈动脉粥样斑块稳定性之间的关系有待进一步研究
4、。 研究目的：I研究MMP一12血清水平与颈动脉粥样硬化斑块稳定性之间的关系； 2探讨MMP1282AG多态性与颈动脉粥样易损斑块的相关性。实验方法：连续收集符合入选标准的2021年7月至2021年7月间在我院神经内科住 院的急性脑梗死患者，根据B超检查定义颈动脉斑块及其分类标准，将颈动脉温州医学院硕士学位论文斑块呈高回声的患者纳入稳定斑块组(n=710)，呈低回声的患者纳入易损斑块组 (n=340)，B超提示无斑块或颈动脉内膜厚度Imm的患者纳入对照组(n=364)。 采用ELISA法测定三组患者的血清MMP12水平，并且运用聚合酶链反响限制 性酶切片段长度多态I生(PCRPLV)方法分析三
5、组患者MMP一12基因启动子82AG多态性。实验结果：1非条件Logistic回归筛选危险因素可见易损斑块组及稳定斑块组间最终进入模型的危险因素是低密度脂蛋白胆固醇，其P=0040，僻1809，95四(1027，3187)。2三组血清MMP12水平分别为稳定斑块组172+72 ngml，易损斑块组16885 ngml，对照组158+87 ngml，三者比拟无统计学意义(产0675， P=0510)，其中稳定斑块组与易损斑块组比拟也无统计学意义(p0755)。3三组AG+GG基因型频率分别为稳定斑块组39，易损斑块组47，对 照组23，三者比拟无统计学差异(矿=1242，P=0537)，且G等位
6、基因频率 之间比拟也无统计学意义(矿=1218，P=-0544)。实验结论：本研究的结果提示血清MMP12水平及其启动子82AG位点多态性均与颈 动脉粥样硬化易损斑块的稳定性之间无明显相关性。关键词：颈动脉动脉粥样硬化；基因多态性；基质金属蛋白酶一12；易损斑块温州医学院硕士学位论文Association of MMP12 Serum Levels and Genetic Polymorphism of-82 AG with Carotid Plaque StabilityAbstract Background：Epidemiological studies indicate that the
7、re are approximately 1 50200 millionnew cases of stroke each year in China；the incidence rate of stroke is approximately (1 1 6-2 1 9)1 0 million people after adjusting for age in the population，and the mortality rate is approximately(58142)10 million people each yearCurrently, there are more than 7
8、00 million patients with cerebrovascular disease；ischemic stroke accounts for approximately 70of these casesAnd with the improvement of living standards，ischemic stroke experienced more and more younger,foreign statistics show that youth stroke incidence rates is high(34I 13)1 0 million people【2】，an
9、d its poor prognosis not only threatens the lives of the patients and life，but also a heavy financial and psychological burden to the family and societyMore and more evidence proves that carotid atherosclerosis and the recurrence of ischemic stroke are closelyrelatedWith further research on atherosc
10、lerosis，there is growing evidence that mostlesions caused ischemic events are not in the narrowest of blood vessels，but areinstead due to atherosclerotic plaque rupture or fissure and thrombosis，resulting inL3lblood vessel blockage Therefore，factors which can affect the stability of carotidplaque ha
11、ve become the focus in the field of ischemic strokeMatrix metalloproteinases(MMPs)are a superfamily of zincdependent proteases，which play a major role in degrading the extracellular matrix(ECM)A large number of studies from domestic and foreign found that MMPs involved in the pathophysiology of athe
12、rosclerosis formation processt 51MMP12(Marix metalloproteinase一1 2)is a key member of the family of MMPs and is secreted by macrophagesMMP一12 displays broad substrate specificity，including extracellular matrix proteins such as elastase，type IV collagen，fibronectin，laminin，glass laminin， proteoglycan
13、s，chondroition sulfate，and myelin basic proteinA number of studieshave shown that MMP12 can promote the progress of atherosclerosis6,71Therefore， it is interesting to explore the association between MMP一1 2 serum levels and thestability of carotid plaqueMMP一1 2 expression is primarily regulated at t
14、he transcriptional levelMMP-1 2-82 AG polymorphisms in the promoter was shown to modulate transcription byafiecting the interaction of nuclear binding proteinsIn a previous study,a common functional MMP-12(-82AG)promoter polymorphism that increases its expression 1S associated with increased coronal
15、y artery stenosis in diabetic patients刚At present，the relationship between MMP。1 282 AG polymorphism and stability of the carotidartery needs further stuayobjeetive：1To explore the relationship between serum level of MMP-1 2 and stability ofcarotid artery plaque2To reveal the possible association of MMP一1 282 AG polymorphisms withstability of the carotid arteryMethods：All of the subjects with cerebral infarctions were patients who were hospitalized20 1 1Based in the Depart
