【作者】 李红；

【导师】 杨林花；

【作者基本信息】 山西医科大学 ， 内科血液病， 2004， 硕士

【摘要】 脑梗塞（cerebral infarction，CI）是指脑部血液供应障碍，缺血、缺氧引起脑组织坏死、软化，出现相应的神经系统症状，常出现偏瘫、失语等。多见于50岁～60岁以上患有动脉粥样硬化的老年人，其以高发病率、高致残率和高死亡率极大地危害着人类的健康。脑梗塞是一种多因素疾病，既有环境因素，又有遗传因素的参与。近年来有关基因多态性和基因突变对脑梗塞的潜在影响已成为一个新的研究领域。基因结构和表达的异常，包括基因的突变、移位、插入、缺失和调控异常可能是其发病的根本原因。目的：探讨脑梗塞患者基质金属蛋白酶-9(matrix metalloproteinase–9 MMP-9)及血小板糖蛋白(glycoprotein GP)IIIa基因多态性与疾病的关系，并检测其血浆纤维蛋白原（fibrinogen, FIB）、同型半胱氨酸（homocysteine ,Hcy）、总胆固醇（total cholesterol，TC）、甘油三酯 （triglyceride，TG）、 低密度脂蛋白（low density lipoprotein， LDL）、 高密度脂蛋白 （high density lipoprotein,HDL）、脂蛋白a （lipoprotein a，LPa）、载脂蛋白A（apolipoprotein A，APOA）、 载脂蛋白 B（apolipoprotein B，APOB）水平。方法：选择2003年8月至2003年12月期间在山西医科大学第二附属医院神经内科住院的脑梗塞患者57例，男39例，女18例，年龄33~82岁，平均67.86±10.20岁；健康对照84例，男52例，女32例，年龄40~74岁，平均62.55±9.22岁，选自健康体检者。采用全自动生化仪对血浆FIB、Hcy、血脂（TC、TG、LDL、HDL、LPa）及载脂蛋白APOA、APOB水平进行检测；KI法提取血细胞DNA，采用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)方法，根据凝胶电泳所见的条带区分各研究对象的基因型，并统计各基因型频率。与健康人上述指标进行比较。结果：脑梗塞患者组血浆TC、TG、LDL、LPa、APOB较对照组增高但均无统计学意义；APOA较对照组降低且具有显著性差异。而脑梗塞患<WP=5>者组血浆FIB及Hcy较对照组显著增高。多因素回归分析中，纤维蛋白原进入回归方程。脑梗塞组MMP-9 C-1562T处等位基因突变频率与正常对照组有显著性差异，而GPIIIa T1565C位点在患者组及对照组的突变频率均很低。结论：血脂及血浆载脂蛋白与脑梗塞的关系有待于进一步证实；血浆纤维蛋白原和同型半胱氨酸水平升高是脑梗塞发病的危险因素；MMP-9C-1562T基因多态性可能是导致脑梗塞后MMP-9表达增加的原因，并引起脑组织的损伤；GPIIIaT1565C与脑梗塞的关系尚待进一步研究。更多还原

【Abstract】 Cerebral infarction (CI) refers to a disease of ischemia that causes the brain tissue necrosis ,soften and the patients often appear corresponding nervous system symptoms such as hemiplegia and aphasia. The person who suffered from the disease is usually more than 50 years old with coronary arteriosclerosis. It has become a great danger to human health with it’s high morbidity and mortality as a kind of multifactor disease that include environmental and inherent factors .In recent years, it has become a new field that researching the potential influence of gene polymorphism and gene mutation to cerebral infarction. The results of the study have illustrated that gene structure and expression abnormal may be the basic reason that causes cerebral infarction, including mutation, shifting, inserting and lacking of the gene.Objective: To study the relevance between the MMP-9 (Matrix metalloproteinase-9) ,GP( Glycoprotein ) IIIa with the disease of cerebral infarction. The level of plasma fibrinogen (FIB), homocysteine(Hcy), lipid such as total cholesterol (TC), triglyceride(TG), low density lipoprotein(LDL), high density lipoprotein (HDL), lipoprotein a(LPa), apolipoprotein A(APOA) and apolipoprotein B(APOB) has been examined.Methods： Fifty-seven patients of cerebral infarction, including 39 male, 18 female are from the Second Hospital of ShanXi Medicine University. The age is from 33 to 82, mean age is 67.86±10.20. Eighty-four healthy person, selected from physical examination,are control group including 52 male, 32 female.The age is from 40 to 74 and the mean age is 62.55±9.22. The level of FIB ,Hcy, lipid ( TC, TG, LDL, HDL, LPa) and apolipoprotein (APOA, APOB) were measured by full-automatic biochemical apparatus. Draw blood cell DNA with potassium iodide(KI) method and distinguish the genotype <WP=7>according to the strip. Compared with the above-mentioned control. Results: The level of plasma TC, TG, LDL, Lpa, APOA , APOB,FIB and Hcy is higher in patients with CI. TC, TG and LDL have no significant difference(p>0.05), while FIB,Hcy are remarkable higher than the control group(p<0.05). Using multifactor analyzing, the plasma level of FIB enters the regression equation. The gene mutation at MMP-9 C-1562T position has remarkable difference, while the mutation at GPIIIaT1565C position is very low in both CI and control group.Conclusion: The relationship between plasma lipid and apolipoprotein with cerebral infarction is not clear and their function is still to be proved in future.Plasma FIB and Hcy are the dangerous factors for the patients with CI. MMP-9 C1562 T gene polymorphism may cause the brain to express high level of MMP-9 and induce brain hurted. The relationship between the polymorphism of GPIIIa T1565C with CI is still to be researched.更多还原