sCD40L、NF-κB、PTX3与脑梗死及CD40基因rs1535045单核苷酸多态性关系的探讨

发布时间：2018-04-21 03:16

本文选题：sCD40L + PTX3　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:1、探讨人外周血可溶性CD40配体(soluble CD40 ligand,s CD40L)、核因子-κB(nuclear factor-κB,NF-κB)及人五聚素3(pentraxin 3,PTX3)表达水平与脑梗死(cerebral infarction,CI)的关系。并探究人外周血s CD40L、NF-κB、PTX3三种炎症因子之间的关联。2、观察CD40基因rs1535045单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)与s CD40L、NF-κB及PTX3之间的关系,探究rs1535045 SNP在动脉硬化形成过程中可能存在的炎症信号通路。方法:在取得知情同意、符合伦理学的标准情况下,选取急性期脑梗死患者90例作为病例组,同时期体检中心健康成年人85名作为对照组。收集血液标本并提取外周血DNA,通过Taq Man探针技术确定rs1535045 SNP基因型,采用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)检测血浆s CD40L、PTX3浓度,采用流式细胞术(flow cytometry,FCM)检测人外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)中NF-κB p65的阳性表达率。比较两组间s CD40L、PTX3及NF-κB表达水平的差异,并分别分析此三种炎症指标两两之间的相关性,及与rs1535045 SNP之间的关系。结果:1、病例组血浆s CD40L浓度为(64.952±19.474)pg/m L,血浆PTX3浓度为(1.957±0.599)ng/m L,PBMCs中NF-κB阳性率为(30.883±12.748)%;对照组血浆s CD40L浓度为(59.176±16.698)pg/m L,PTX3浓度为(1.737±0.632)ng/m L,PBMCs中NF-κB阳性率为(18.082±8.674)%。病例组血浆s CD40L、PTX3浓度及PBMCs中NF-κB阳性表达率均显著高于对照组,差异有统计学意义(P0.05)。2、全部样本中s CD40L血浆水平与NF-κB阳性率之间存在正相关(r=0.485,p0.001),s CD40L与PTX3血浆水平之间存在正相关(r=0.251,P=0.001),NF-κB与PTX3表达水平之间存在正相关(r=0.301,P0.001)。分层分析病例亚组s CD40L血浆水平与NF-κB阳性率之间存在正相关(r=0.764,P0.001),s CD40L与PTX3血浆水平之间存在正相关(r=0.445,P0.001),NF-κB与PTX3表达水平之间存在正相关(r=0.384,P0.001)。对照组亚中,尚不能认为s CD40L血浆水平与NF-κB阳性率之间存在相关性,P=0.716;尚不能认为s CD40L与PTX3血浆水平存在相关性,P=0.867;尚不能认为NF-κB阳性表达率与PTX3血浆水平之间存在相关性,P=0.558。故尚不能认为此3种炎症因子两两之间存在相关性。3、CD40基因rs1535045 CC基因型、CT基因型、TT基因型的s CD40L浓度分别为(59.555±18.070)pg/ml、(63.453±17.193)pg/ml、(65.278±23.545)pg/ml,NF-κB p65阳性率分别为(22.671±11.183)%、(25.365±12.287)%、(28.400±17.757)%,血浆PTX3浓度分别为(1.810±0.610)ng/ml、(1.863±0.609)ng/ml、(1.927±0.745)ng/ml,3种基因型组间差异均无统计学意义,但有浓度梯度。分层分析脑梗死病例组及对照组的3种基因型之间的血浆s CD40L浓度、PTX3浓度及NF-κB p65阳性率的分布差异无统计学意义(P0.05)。进一步分析病例组中动脉粥样硬化型脑梗死亚组的3种基因型在血浆s CD40L浓度、PTX3浓度及NF-κB p65阳性率的分布差异仍无统计学意义(P0.05),但亦存在较明显的浓度梯度。结论:1.急性期脑梗死患者体内s CD40L、PTX3血浆浓度及NF-κB阳性率均显著升高,且此三种炎性因子两两之间均呈正相关。2.尚不能认为rs1535045 SNP与s CD40L、NF-κB及PTX3表达水平之间存在关系。
[Abstract]:Objective: 1, to explore the relationship between human peripheral blood soluble CD40 ligand (soluble CD40 ligand, s CD40L), nuclear factor kappa B (nuclear factor- kappa B, NF- kappa B) and human five poly (3), and to explore the correlation between human peripheral blood and three kinds of inflammatory factors. The relationship between the rs1535045 single nucleotide polymorphism (Single Nucleotide Polymorphisms, SNP) and s CD40L, NF- kappa B and PTX3 to explore the possible inflammatory signaling pathway in the formation of arteriosclerosis by rs1535045 SNP. Methods: 90 cases of acute cerebral infarction were selected as the standard of informed consent and ethical standards. In the case group, 85 healthy adults at the same time physical examination center were used as the control group. The blood samples were collected and the peripheral blood DNA was extracted. The rs1535045 SNP genotype was determined by the Taq Man probe technique. The s CD40L of the plasma was detected by the enzyme linked immunosorbent assay (enzyme-linked immunosorbent assay, ELISA), and the PTX3 concentration was carried out by flow cytometry. The positive rate of NF- kappa B p65 in human peripheral blood mononuclear cells (peripheral blood mononuclear cells, PBMCs) was detected by try, FCM. The difference between the s CD40L and the expression level of the two groups was compared, and the correlation between the three inflammatory indices 22 and the relationship between them were analyzed. The concentration of L was (64.952 + 19.474) pg/m L, the plasma PTX3 concentration was (1.957 + 0.599) ng/m L, the positive rate of NF- kappa B in PBMCs was (30.883 + 12.748)%, and s CD40L concentration in the control group was (59.176 + 16.698) pg/m, and the concentration was (1.737 + 0.632). The positive rate of the positive expression was significantly higher than that in the control group (P0.05).2. There was a positive correlation between the plasma level of s CD40L and the positive rate of NF- kappa B in all samples (r=0.485, p0.001), and there was a positive correlation between s CD40L and PTX3 plasma level. There was a positive correlation between the plasma level of s CD40L and the positive rate of NF- kappa B (r=0.764, P0.001), and there was a positive correlation between the level of s CD40L and PTX3 plasma level (r=0.445, P0.001), and there was a positive correlation between the NF- kappa and the expression level. In correlation, P=0.716, it is not yet believed that there is a correlation between s CD40L and PTX3 plasma levels, P=0.867, and there is no correlation between the positive expression rate of NF- kappa B and the plasma level of PTX3, and P=0.558. is not considered to be associated with the correlation of.3, CD40 gene, genotype, and genotype. The concentration of D40L was (59.555 + 18.070) pg/ml, (63.453 + 17.193) pg/ml, (65.278 + 23.545) pg/ml, and the positive rates of NF- kappa B p65 were (22.671 + 11.183)%, (25.365 + 12.287)%, (28.400 + 17.757)%, and the plasma PTX3 concentration was (1.810 +%) ng/ml and ng/ml, and there was no statistical difference between the genotypes. But there was a concentration gradient. There was no significant difference in plasma s CD40L concentration, PTX3 concentration and NF- kappa B p65 positive rate between 3 genotypes in cerebral infarction case group and control group (P0.05). Further analysis of the concentration of s CD40L, PTX3 concentration and NF- kappa in the 3 genotypes of atherosclerotic cerebral infarction subgroup in the case group There was no significant difference in the distribution of B p65 positive rates (P0.05), but there was also a significant concentration gradient. Conclusion: 1. the s CD40L, PTX3 plasma concentration and the positive rate of NF- kappa B in patients with acute cerebral infarction were significantly increased, and the positive correlation between the three inflammatory factors 22 was not considered as rs1535045 SNP and S. There is a relationship between the level of expression.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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