基质金属蛋白酶-9基因多态性与高血压脑出血患者迟发性脑水肿的相关性研究
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摘要
目的探讨基质金属蛋白酶-9(MMP-9)基因多态性与高血压脑出血(HICH)患者迟发性脑水肿的关系。方法选择2015年1月至2017年10月于本院神经内科行内科保守治疗的137例HICH患者,按照是否合并迟发性脑水肿分为观察组42例和对照组95例,采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测MMP-9基因-1562C/T多态性,并收集患者临床资料进行统计学分析。结果两组患者在年龄、糖尿病、持续发热、基线血肿体积和基线NIHSS评分方面差异均具有统计学意义(均P<0.05)。观察组血清MMP-9水平显著高于对照组[(176.7±50.3) mg/L vs(145.8±41.3)mg/L,P=0.000]。MMP-9基因-1562C/T位点CC基因型患者血清MMP-9水平显著低于(CT+TT)基因型的患者[(147.3±45.0) mg/L vs (189.2±59.4) mg/L,P=0.000]。与对照组比较,观察组T等位基因分布频率显著增加(P=0.019)。多因素Logistic回归分析结果显示携带MMP-9基因-1562C/T位点T等位基因是HICH患者发生迟发型脑水肿的危险因素(OR=2.612,95%CI:1.187～6.670,P=0.005)。结论 MMP-9基因-1562C/T多态性可能与HICH患者迟发型脑水肿发生相关。
Objective To investigate the relationship between matrix metalloproteinase-9(MMP-9) gene polymorphism and delayed cerebral edema in patients with hypertensive intracerebral hemorrhage(HICH).Methods 137 HICH patients were recruited to participate in the study.According to whether combined with delayed cerebral edema,they were divided into the case group(42 cases) and the control group(95 cases).Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-FLP) for MMP-9 gene-1562 C/T polymorphism.Clinical data was collected for statistical analysis.Results There was significant difference in age,diabetes,persistent fever,baseline hematoma volume and National Institute of Health Stroke Scale(NIHSS) between the case group and the control group(all P <0.05).Meanwhile,serum MMP-9 level of the case group was significantly higher than that of the control group [(176.7 ±50.3)mg/L vs(145.8 ±41.3)mg/L,P=0.000].There were significant difference in serum MMP-9 level between genotype CC and genotype(CT + TT) [(147.3 ± 45.0)mg/L vs(189.2 ±59.4)mg/L,P =0.000].Compared with the control group,the distribution frequencies of allele T in the case group was significantly increased(P = 0.019).Multivariate Logistic regression analysis showed that Allele T was a risk factor of delayed cerebral edema for HICH patients(OR = 2.612,95% CI:1.187-6.670,P=0.005).Conclusions For spontaneous HICH patients,MMP-9 gene-1562 C/T polymorphism may closely related to delayed cerebral edema.
Objective To investigate the relationship between matrix metalloproteinase-9(MMP-9) gene polymorphism and delayed cerebral edema in patients with hypertensive intracerebral hemorrhage(HICH).Methods 137 HICH patients were recruited to participate in the study.According to whether combined with delayed cerebral edema,they were divided into the case group(42 cases) and the control group(95 cases).Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-FLP) for MMP-9 gene-1562 C/T polymorphism.Clinical data was collected for statistical analysis.Results There was significant difference in age,diabetes,persistent fever,baseline hematoma volume and National Institute of Health Stroke Scale(NIHSS) between the case group and the control group(all P <0.05).Meanwhile,serum MMP-9 level of the case group was significantly higher than that of the control group [(176.7 ±50.3)mg/L vs(145.8 ±41.3)mg/L,P=0.000].There were significant difference in serum MMP-9 level between genotype CC and genotype(CT + TT) [(147.3 ± 45.0)mg/L vs(189.2 ±59.4)mg/L,P =0.000].Compared with the control group,the distribution frequencies of allele T in the case group was significantly increased(P = 0.019).Multivariate Logistic regression analysis showed that Allele T was a risk factor of delayed cerebral edema for HICH patients(OR = 2.612,95% CI:1.187-6.670,P=0.005).Conclusions For spontaneous HICH patients,MMP-9 gene-1562 C/T polymorphism may closely related to delayed cerebral edema.
引文
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[8] Fan ZZ, Ge ZM, Cai HB, et al.Association between the MMP-9-1562 C>T polymorphism and the risk of stroke:a meta-analysis[J].Mol Biol Rep, 2014,41(10):6787-6794.DOI:10.1007/s11033-014-3564-0.
[9]杭军,周家强,温大平,等.外周血内皮祖细胞在高血压性脑出血不同时期患者中的动态变化分析[J].中国医师杂志,2016,18(6):871-874.DOI:10.3760/cma.j.issn.1008-1372.2016.06.019.
[10]邓榕,刘勇,宋媛媛,等.脑出血微创引流术后经颅多普勒超声动态监测和CT动态扫描的对照研究[J].中国医师杂志,2017,19(3):450-452.DOI:10.3760/cma.j.issn.1008-1372.2017.03.038.
[11]宛丰,黄梅,吕衍文,等.MMP-9与脑出血后迟发性脑水肿的关系研究[J].卒中与神经疾病,2014,21(2):110-112.DOI:10.3969/j.issn.1007-0478.2014.02.016.
[12]岳蕴华,白旭东,张小宁,等.基质金属蛋白酶9血清水平及基因-1562C>T多态性与维吾尔族急性缺血性脑卒中临床分型的关系[J].中国动脉硬化杂志,2014,22(1):55-60.
[13]顾双双,张均,韩玲,等.脑出血后迟发性脑水肿与血浆基质金属蛋白酶9等相关因素的分析[J].中国脑血管病杂志,2015,12(6):297-301.DOI:10.3969/j.issn.1672-5921.2015.06.007.
[14] Feiler S, Plesnila N, Thal SC, et al.Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage[J].Cerebrovase Dis,2011,32(3):289-295.DOI:10.1159/000328248.
[15]唐蕾,王红星,徐晓玉,等.基质金属蛋白酶-9基因多态性与长沙地区汉族人群脑出血的关系研究[J].中国现代医学杂.志,2015,25(10):36-39.
[2]彭形,罗超,肖刚,等.高血压脑出血患者急性期血清TSP1/2、MMP2/9与脑血肿量及脑水肿量的关系研究[J].重庆医科大学学报,2017,42(12):1649-1652.
[3] Masuda Y, Ishikawa E, Yamamoto T, et al.Early Postoperative Expalsion of Parenchymal High-intensity Areas on T2-weighted Imaging Predicts Delayed Cerebral Edema Caused by Carmustine Wafer Implantation in Patients with High-grade Glioma[J].Magn Reson Med Sci, 2016,15(3):299-307.DOI:10.2463/mrms.mp.2015-0054.
[4] Kofler M,Schiefecker A,Ferger B, et al.Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage[J].Neurocrit Care, 2015,23(3):321-329.DOI:10.1007/s12028-015-0140-y.
[5] Li M, Ma RN, Li LH, et al.Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4[J].Eur J Pharmacol, 2013,715(1-3):189-195.DOI:10.1016/j.ejphar.2013.05.022.
[6] Zhou QB, Jin YL, Jia Q, et al.Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage[J].Inflammation,2014,37(1):107-115.DOI:10.1007/s10753-013-9717-9.
[7] Yang J, Wu B, Lin S, et al.Genetic variations of MMP9 gene and intracerebral hemorrhage susceptibility:a case-control study in Chinese Han population[J].J Neurol Sci, 2014,341(1-2):55-57.DOI:10.1016/j.jns.2014.03.049.
[8] Fan ZZ, Ge ZM, Cai HB, et al.Association between the MMP-9-1562 C>T polymorphism and the risk of stroke:a meta-analysis[J].Mol Biol Rep, 2014,41(10):6787-6794.DOI:10.1007/s11033-014-3564-0.
[9]杭军,周家强,温大平,等.外周血内皮祖细胞在高血压性脑出血不同时期患者中的动态变化分析[J].中国医师杂志,2016,18(6):871-874.DOI:10.3760/cma.j.issn.1008-1372.2016.06.019.
[10]邓榕,刘勇,宋媛媛,等.脑出血微创引流术后经颅多普勒超声动态监测和CT动态扫描的对照研究[J].中国医师杂志,2017,19(3):450-452.DOI:10.3760/cma.j.issn.1008-1372.2017.03.038.
[11]宛丰,黄梅,吕衍文,等.MMP-9与脑出血后迟发性脑水肿的关系研究[J].卒中与神经疾病,2014,21(2):110-112.DOI:10.3969/j.issn.1007-0478.2014.02.016.
[12]岳蕴华,白旭东,张小宁,等.基质金属蛋白酶9血清水平及基因-1562C>T多态性与维吾尔族急性缺血性脑卒中临床分型的关系[J].中国动脉硬化杂志,2014,22(1):55-60.
[13]顾双双,张均,韩玲,等.脑出血后迟发性脑水肿与血浆基质金属蛋白酶9等相关因素的分析[J].中国脑血管病杂志,2015,12(6):297-301.DOI:10.3969/j.issn.1672-5921.2015.06.007.
[14] Feiler S, Plesnila N, Thal SC, et al.Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage[J].Cerebrovase Dis,2011,32(3):289-295.DOI:10.1159/000328248.
[15]唐蕾,王红星,徐晓玉,等.基质金属蛋白酶-9基因多态性与长沙地区汉族人群脑出血的关系研究[J].中国现代医学杂.志,2015,25(10):36-39.