發(fā)布時間：2018-12-13 03:14

【摘要】：目的探討多發(fā)性硬化患者外周血CD4T淋巴細胞LFA-1啟動子序列甲基化狀態(tài)是否存在異常；同時探究甲基化狀態(tài)的異常是否與患者病情嚴重程度及預(yù)后因素相關(guān)，明確甲基化狀態(tài)的改變能否作為病情診斷及預(yù)后判斷的指標。方法選擇臨床診斷明確、處于發(fā)病急性期且未接受免疫抑制或免疫調(diào)節(jié)治療的緩解復發(fā)型多發(fā)性硬化患者21名，留取其血液標本，，記錄其發(fā)病全過程及本次發(fā)病時擴展的殘疾狀況量表(expanded disability status scale,EDSS)評分，并行腰椎穿刺及頭顱MRI增強掃描檢查；21名患者中有11名曾于緩解期于我院住院復查，再次留取外周血標本，共計32例血液標本納入實驗組。選擇與患者年齡、性別相匹配的健康者32名，同樣留取外周血標本納入對照組。檢測血標本中CD4T淋巴細胞CD11a表達基因啟動子序列甲基化狀態(tài)，并進行對照分析。結(jié)果在整體的血標本檢測中，多發(fā)性硬化患者CD4T淋巴細胞CD11a表達基因啟動子序列甲基化狀態(tài)與正常對照相比，二者間并不存在顯統(tǒng)計學差異（p＞0.05）；但對于處發(fā)病急性期患者的那部分血標本其甲基化狀態(tài)要低于正常對照組（p＜0.05）；同時對于同一患者，處發(fā)病急性期時其甲基化狀態(tài)要較處緩解期時低（p＜0.05）；但患者DNA甲基化狀態(tài)與首發(fā)癥狀是否有括約肌功能障礙、首次發(fā)作與第二次發(fā)作時間間隔長短、腦脊液寡克隆帶是否陽性、頭顱MRI是否出現(xiàn)出現(xiàn)環(huán)形強化、EDSS評分的高低及患病病程長短等臨床特征并不存在相關(guān)性（p＞0.05）。結(jié)論CD4T淋巴細胞CD11a表達基因啟動子序列甲基化狀態(tài)至少與多發(fā)性硬化的發(fā)病狀態(tài)相關(guān)，且這種甲基化狀態(tài)的改變與標本的冷凍保存無關(guān)；但甲基化狀態(tài)的差異并不能反映發(fā)病時的病情嚴重程度或作為判斷預(yù)后的指標；同時目前仍不能明確這種甲基化狀態(tài)的改變與多發(fā)性硬化發(fā)病存在何種關(guān)聯(lián)。
[Abstract]:Objective to investigate whether there is abnormal methylation of LFA-1 promoter sequence in peripheral CD4T lymphocytes of patients with multiple sclerosis. At the same time, to explore whether the abnormal methylation status is related to the severity of the patient's condition and prognostic factors, and to determine whether the change of the methylation state can be used as an indicator of the diagnosis and prognosis of the disease. Methods A total of 21 patients with relapsed multiple sclerosis (MS) with definite clinical diagnosis and no immunosuppressive or immunomodulatory therapy were selected and their blood samples were collected. The (expanded disability status scale,EDSS scores of the whole course of the disease and the extended disability status scale were recorded, and the lumbar puncture and cranial MRI enhanced scanning were performed. Of the 21 patients, 11 had been reexamined in our hospital during remission period, and 32 blood samples were collected from the experimental group. Thirty-two healthy subjects matched with age and sex were enrolled in the control group. The methylation status of promoter sequence of CD11a expression gene in CD4T lymphocytes was detected and compared. Results in the whole blood samples, there was no significant difference between the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes of patients with multiple sclerosis and that of normal controls (p > 0. 05). However, the methylation status of the blood samples of the patients in the acute stage of the disease was lower than that of the normal control group (p < 0.05). At the same time, the methylation status of the patients in the acute stage was lower than that in the remission stage (p < 0.05). However, whether there were sphincter dysfunction, the interval between the first episode and the second episode, the positive oligoclonal bands in cerebrospinal fluid, and the circular enhancement of cranial MRI were found in the patients with DNA methylation and initial symptoms. There was no correlation between the EDSS score and the duration of the disease (p > 0. 05). Conclusion the methylation status of the promoter sequence of CD11a expression gene in CD4T lymphocytes is at least related to the pathogenesis of multiple sclerosis, and the change of this methylation state is not related to the cryopreservation of the specimens. However, the difference of methylation status can not reflect the severity of the disease at the time of onset or as a prognostic indicator, and it is still not clear how the change of methylation status is associated with the pathogenesis of multiple sclerosis.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R744.51

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