發(fā)布時(shí)間：2018-05-23 19:17

  本文選題：脫髓鞘疾病趨化因子 + CXCL13　； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的探討中樞神經(jīng)系統(tǒng)(CNS)炎性脫髓鞘疾病相關(guān)的一些新型生物標(biāo)記物,包括B細(xì)胞趨化因子CXCL13、神經(jīng)絲蛋白輕鏈(NFL)、25-羥基維生素D3[25(OH)D3]的表達(dá)特點(diǎn)及其與臨床、影像的關(guān)系,探討維生素D受體基因(VDR)、水通道蛋白4(AQP4)基因、Fc受體樣3(Fc RL3)基因單核苷酸多態(tài)性(SNPs)突變情況,為CNS炎性脫髓鞘疾病發(fā)病機(jī)制的探索、鑒別診斷和臨床轉(zhuǎn)歸提供依據(jù)。方法收集就診于海軍總醫(yī)院神經(jīng)內(nèi)科的CNS炎性脫髓鞘疾病患者及正常對(duì)照(NC),收集實(shí)驗(yàn)組臨床、影像信息及各組血清、全血和腦脊液(CSF)標(biāo)本,以酶聯(lián)免疫吸附實(shí)驗(yàn)(ELISA)方法檢測(cè)血清和CSF中CXCL13水平及CSF中NFL水平,以質(zhì)譜法檢測(cè)血清25(OH)D3水平,以第一代基因測(cè)序方法檢測(cè)VDR基因、AQP4基因和Fc RL3基因SNPs序列。結(jié)果(1)CIS組、MS組、NMOSD組血清和CSF中CXCL13水平均高于NC組(P0.05)。NMOSD組血清和CSF中CXCL13水平明顯高于CIS組和MS組(P0.05),MS組CSF中CXCL13水平明顯高于CIS組(P0.05)。CIS組、MS組、NMOSD組CSF中CXCL13水平分別與其EDSS評(píng)分和MRI上病灶強(qiáng)化相關(guān)(P0.05)。(2)CIS組、MS組、NMOSD組CSF中NFL水平均高于NC組(P0.05)。CIS組、MS組、NMOSD組組間CSF中NFL水平無顯著統(tǒng)計(jì)學(xué)差異(P0.05)。CIS組、MS組、NMOSD組CSF中NFL水平與其EDSS評(píng)分和MRI上病灶強(qiáng)化相關(guān)(P0.05)。(3)CIS組、MS組、NMOSD組血清25(OH)D3水平均明顯低于NC組(P0.05)。CIS組、MS組、NMOSD組組間血清25(OH)D3水平比較無顯著統(tǒng)計(jì)學(xué)差異(P0.05)。CIS組、MS組、NMOSD組組間血清25(OH)D3水平與EDSS評(píng)分和CSF中NFL水平無明顯相關(guān)(P0.05)。(4)CIS組、MS組、NMOSD組VDR基因rs2228570位點(diǎn)突變率明顯高于NC組,且具有統(tǒng)計(jì)學(xué)差異(P0.05)。CIS組、NMOSD組rs7975232位點(diǎn)突變率明顯高于NC組,且具有統(tǒng)計(jì)學(xué)差異(P0.05);MS組rs7975232位點(diǎn)突變率高于NC組,但無統(tǒng)計(jì)學(xué)差異(P0.05)。(5)CIS組、MS組、NMOSD組AQP4基因rs2075575、rs3763043、rs14393位點(diǎn)突變率分別與NC組比較均無統(tǒng)計(jì)學(xué)差異(P0.05);NMOSD組AQP4-Ab陽性與否對(duì)AQP4基因SNPs亦無影響(P0.05)。(6)CIS組、NMOSD組Fc RL3基因rs7528684和rs3761959位點(diǎn)突變率明顯高于NC組,且具有統(tǒng)計(jì)學(xué)差異(P0.05);MS組rs7528684和rs3761959位點(diǎn)突變率高于NC組,但無統(tǒng)計(jì)學(xué)差異(P0.05)。MS組、NMOSD組rs945635位點(diǎn)突變率明顯高于NC組,且具有統(tǒng)計(jì)學(xué)差異(P0.05);CIS組rs945635位點(diǎn)突變率高于NC組,但無統(tǒng)計(jì)學(xué)差異(P0.05)。結(jié)論CSF中CXCL13水平和CSF中NFL水平是預(yù)測(cè)CIS、MS和NMOSD的殘障程度及疾病活動(dòng)性的生物學(xué)指標(biāo)。CIS、MS和NMOSD患者均存在維生素D缺乏,但其血清25(OH)D3水平與殘障程度不相關(guān)。VDR基因rs7975232和rs2228570位點(diǎn)突變、Fc RL3基因rs7528684、rs945635和rs3761959位點(diǎn)突變可增加CIS、MS、NMOSD患者發(fā)病風(fēng)險(xiǎn),但對(duì)區(qū)分CNS炎性脫髓鞘疾病的種類和判斷其轉(zhuǎn)歸均無明顯作用。AQP4基因SNPs對(duì)CIS、MS、NMOSD患者發(fā)病無明顯影響。
[Abstract]:Objective to investigate the expression characteristics of neurofilament light chain protein (NFL) 25-hydroxyvitamin D _ 3 (25(OH)D3) and its relationship with clinical and imaging features, including B cell chemokine CXCL13, neurofilament protein light chain, and some novel biomarkers associated with inflammatory demyelinating disease in central nervous system (CNS). To investigate the mutations of vitamin D receptor gene (VDR), aquaporin-4 (aquaporin-4) gene, FC-like 3(Fc RL3) gene and single nucleotide polymorphisms (SNPs) in order to explore the pathogenesis of CNS inflammatory demyelinating disease and to provide evidence for differential diagnosis and clinical outcome. Methods the clinical, imaging information and serum, whole blood and cerebrospinal fluid (CSF) samples of patients with CNS inflammatory demyelinating disease and normal control group were collected from Department of Neurology, Naval General Hospital. The levels of CXCL13 in serum and CSF and NFL in CSF were detected by Elisa, 25(OH)D3 in serum were detected by mass spectrometry, and SNPs sequences of VDR and FC RL3 genes were detected by first-generation gene sequencing. Results the levels of CXCL13 in serum and CSF in MS group were higher than those in NMOSD group in NC group (P 0.05). CXCL13 in CSF group was significantly higher than that in CSF in CIS group and MS group (P 0.05). CXCL13 level in CSF in MS group was significantly higher than that in CIS group (P 0.05). The CXCL13 level in CSF in MS group was significantly higher than that in CIS group. The NFL level in CSF of MS group was higher than that of NC group P0.05 +. Cis group. There was no significant difference in NFL level between MS group and NMOSD group (P0.05). NFL level in CSF, EDSS score and enhancement of MRI in MS group were higher than those in NMOSD group (P 0.05 ~ 0. 05, P < 0. 05), and there was no significant difference in NFL level between NMOSD group and MS group (P 0. 05, P 0. 05, P < 0. 05, P < 0. 05). There was no significant difference in serum 25(OH)D3 level between MS group and EDSS score and NFL level in CSF. There was no significant difference in serum 25(OH)D3 level between MS group and NMOSD group (P 0.05). There was no significant difference in serum 25(OH)D3 level between MS group and EDSS group and NFL level in CSF in MS group and in CSF group. There was no significant difference in serum 25(OH)D3 level between MS group and NC group (P 0.05, P 0.05). There was no significant difference in serum 25(OH)D3 level with EDSS score and NFL level in CSF between MS group and EDSS group in CIS group. There was no significant difference in serum 25(OH)D3 level between NMOSD group and MS group. The mutation rate of VDR rs2228570 locus in MS group was significantly higher than that in NC group. The mutation rate of rs7975232 locus in NMOSD group was significantly higher than that in NC group, and the mutation rate of rs7975232 locus in MS group was higher than that in NC group. However, there was no significant difference in the mutation rate of rs20755775, rs3763043, rs14393 in AQP4 gene between MS group and NC group. There was no significant difference between P0.05NMOSD group and NC group. There was no significant difference in AQP4-Ab positive rate of AQP4 gene SNPs between NMOSD group and NC group. The mutation rates of rs7528684 and rs3761959 locus of FC RL3 gene in NMOSD group were significantly higher than those in NC group. The mutation rate of rs7528684 and rs3761959 in MS group was higher than that in NC group, but the mutation rate of rs945635 locus in P0.05 + MS group was significantly higher than that in NC group, and the mutation rate of rs945635 locus in P0.05 + MS group was higher than that in NC group, but there was no statistical difference (P0.05). Conclusion the levels of CXCL13 in CSF and NFL in CSF are biological indexes for predicting the degree of disability and disease activity of CISMS and NMOSD. There is vitamin D deficiency in patients with CISMS and NMOSD. However, the level of serum 25(OH)D3 was not related to the degree of disability. The mutation of rs7975232 and rs2228570 locus of rs2228570 gene Fc RL3 gene rs7528684 rs945635 and rs3761959 locus increased the risk of NMOSD patients. AQP4 gene SNPs had no significant effect on the classification and prognosis of CNS inflammatory demyelinating diseases. There was no significant effect of AQP4 gene SNPs on the pathogenesis of CNS.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R744.5

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