【作者】 王敏；

【导师】 梁成；

【作者基本信息】 兰州大学 ， 临床医学·神经病学（专业学位）， 2022， 硕士

【摘要】 研究目的探究前循环大面积脑梗死患者急性期血清淋巴细胞及炎症因子水平差异以及与病情严重程度的相关性,探索血清淋巴细胞及炎症因子对前循环大面积梗死患者短期预后的评估价值。研究方法本研究为病例对照研究,根据纳入和排除标准,选取2020年12月-2021年12月我院NICU收治的前循环大面积梗死患者61例作为病例组,纳入同期健康体检者46例作为对照组。收集病例组性别、年龄、发病5天内最大NIHSS评分、28天生存情况、是否发生恶性脑水肿、发病48小时内血清总T淋巴细胞、CD4~+T细胞、CD8~+T细胞、总B淋巴细胞、CD4~+/CD8~+、血清炎症因子(IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12P70、TNF-α、IFN-γ、IFN-α、IL-17A),收集对照组年龄、性别、血清淋巴细胞、炎症因子等资料。1、比较病例组与对照组血清淋巴细胞、炎症因子的差异;2、以前循环大面积梗死患者发病5天内最大NIHSS评分为依据,将病例组分为非重症组:NIHSS<15分,重症组:NIHSS≥15分,比较分析两组间血清淋巴细胞与炎症因子水平的差异及与前循环大面积脑梗死病情严重程度的相关性;3、以患者是否发生恶性脑水肿,将患者分为恶性脑水肿组和非恶性脑水肿组,比较分析两组血清淋巴细胞与细胞因子的差异;4、根据患者发病28天生存情况,将患者分为死亡组与存活组,比较分析两组血清淋巴细胞与炎症因子差异,通过多因素二元Logistics回归分析筛选前循环大面积脑梗死发病28天死亡影响因素;5、绘制发病28天死亡影响因素ROC曲线,探究前循环大面积脑梗死后淋巴细胞中对死亡最佳预测指标及临界值,灵敏度和特异度。结果1.前循环大面积脑梗死组与非脑梗死组比较,前循环大面积脑梗死组血清总T淋巴细胞、CD4~+T细胞、CD4~+/CD8~+较对照组降低,差异具有统计学意义(均P<0.05),病例组总B淋巴细胞、IL-1β、IL-2、IL-6、IL-8、IL-10、IL-12P70、TNF-α、IFN-α、IL-17A较对照组升高,差异具有统计学意义(均P<0.05);2.前循环大面积脑梗死重症组与非重症组比较,重症组血清总T淋巴细胞、CD4~+T细胞、CD4~+/CD8~+较非重症组降低,差异具有统计学意义(均P<0.05),重症组IL-1β、IL-4、IL-6、IL-10、TNF-α较非重症组升高,差异具有统计学意义(均P<0.05),血清总T淋巴细胞亚群、CD4~+T细胞亚群、CD4~+/CD8~+水平与NIHSS评分呈负相关,血清IL-1β、IL-6、IL-10、TNF-α水平与NIHSS评分呈正相关。3.前循环大面积脑梗死恶性脑水肿组与非恶性脑水肿相比,恶性脑水肿组血清总T淋巴细胞、CD4~+T细胞、CD4~+/CD8~+较非恶性脑水肿组降低,CD8~+T细胞亚群、TNF-α较非恶性脑水肿组升高,差异具有统计学意义(均P<0.05)。4.前循环大面积脑梗死死亡组与存活组比较,死亡组血清总T淋巴细胞、CD4~+T细胞、CD4~+/CD8~+降低,IL-6、TNF-α升高,差异具有统计学意义(均P<0.05),发病28天死亡影响因素的二元logistics回归分析:血清CD4~+T细胞、CD4~+/CD8~+有统计学意义,校正年龄、性别后,二元Logistics分析结果显示,血清CD4~+/CD8~+是发病28天死亡的独立危险因素。5.血清CD4~+/CD8~+对前循环大面积梗死发病28天死亡预测的ROC曲线分析:CD4~+/CD8~+对前循环大面积梗死发病28天死亡具有预测价值,临界值:1.235,AUC:0.742,95%CI:0.602～0.882,敏感度:0.818,特异度:0.677,P值<0.05。结论1.前循环大面积脑梗死患者急性期血清适应性细胞免疫功能降低,主要表现为血清总T淋巴细胞、CD4~+T淋巴细胞、CD4~+/CD8~+降低,降低程度与病情严重程度呈正相关;2.前循环大面积脑梗死患者急性期血清促炎和抗炎细胞因子均有升高,以促炎细胞因子升高为主;3.CD4~+/CD8~+是前循环大面积脑梗死患者发病28天死亡的独立危险因素,当CD4~+/CD8~+小于1.235时,患者死亡风险增加。更多还原

【Abstract】 ObjectiveTo explore the differences in the levels of serum lymphocytes and inflammatory factors in patients with large-area anterior circulation infarction in the acute stage and their correlation with the severity of the disease,and to explore the value of serum lymphocytes and inflammatory factors in evaluating the short-term prognosis of patients with large-area anterior circulation infarction.MethodThis study is a case-control study.According to the inclusion and exclusion criteria,61 patients with large-area anterior circulation infarction admitted to NICU in our hospital from December 2020 to December 2021 were selected as the case group,and 46 healthy subjects were included in the same period as the control group.The sex,age,maximum NIHSS score within 5 days of onset,28 days of survival,whether malignant brain edema occurred,total T lymphocytes,CD4~+T cells,CD8~+Tcells,total B lymphocytes,CD4~+/CD8~+and serum inflammatory factor(IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12P70、TNF-α、IFN-γ、IFN-α、IL-17A)within 48hours of onset were collected,age,sex,serum lymphocytes,inflammatory factors and other data of the control group were collected.1.The differences of serum lymphocytes and inflammatory factors between the case group and the control group were compared;2.Based on the maximum NIHSS score within 5 days after the onset of large-scale anterior circulation infarction,the case group was divided into non severe group:NIHSS<15 points,severe group:NIHSS≥15 points.The differences in the levels of serum lymphocytes and inflammatory factors between the two groups and the correlation with the severity of large-scale anterior circulation infarction were compared and analyzed;3.The patients were divided into malignant brain edema group and non malignant brain edema group according to whether they had malignant brain edema.The differences of serum lymphocytes and cytokines between the two groups were compared and analyzed;4.The patients were divided into death group and survival group according to the 28 day survival of the patients.The differences of serum lymphocytes and inflammatory factors between the two groups were compared and analyzed.The influencing factors of 28 day death of large area cerebral infarction in anterior circulation were screened by multivariate binary logistic regression analysis;5.Draw the ROC curve of the influencing factors of death on the 28th day after onset,and explore the best predictive index,critical value,sensitivity and specificity of lymphocytes after large-area cerebral infarction in the anterior circulation.Result1.Compared with the non cerebral infarction group,the serum total T lymphocytes,CD4~+T cells and CD4~+/CD8~+in the large area cerebral infarction group were significantly lower than those in the control group(all P<0.05),IL-1β、IL-2、IL-6、IL-8、IL-10、IL-12P70、TNF-α、IFN-α、IL-17A was significantly higher than that in the control group(all P<0.05);2.Compared with the non severe group,the serum total T lymphocytes,CD4~+T cells and CD4+/CD8+in the severe group were significantly lower than those in the non severe group(all P<0.05)β、IL-4、IL-6、IL-10、TNF-αCompared with the non severe group,the difference was statistically significant(all P<0.05).The levels of serum total T lymphocyte subsets,CD4~+T cell subsets and CD4~+/CD8~+were negatively correlated with NIHSS score,and serum IL-1β、IL-6、IL-10、TNF-αThe level was positively correlated with NIHSS score.3.Compared with the non malignant brain edema group,the total T lymphocytes,CD4~+Tcells,CD4~+/CD8~+in the malignant brain edema group were lower than those in the non malignant brain edema group,and the CD8+T cell subsets and TNF-αCompared with non malignant brain edema group,the difference was statistically significant(all P<0.05)..4.Compared with the survival group,the serum total T lymphocytes,CD4~+T cells,CD4~+/CD8~+in the death group decreased,IL-6 and TNF-αincreased.The difference was statistically significant(all P<0.05).Binary logistic regression analysis of the influencing factors of death on the 28th day of onset:Serum CD4~+T cells and CD4~+ / CD8~+ were statistically significant.After adjusting for age and gender,the results of binary logistic analysis showed that serum CD4~+/CD8~+was an independent risk factor of death on the 28th day of onset.5.ROC curve analysis of serum CD4~+/CD8~+in predicting 28 day death after large-scale anterior circulation infarction:CD4~+/CD8~+has predictive value for 28day death after large-scale anterior circulation infarction,the critical value is 1.235,AUC:0.742,95%CI:0.602～0.882,sensitivity:0.818,specificity:0.677,P<0.05.Conclusion1.In patients with massive anterior circulation cerebral infarction,the serum adaptive cellular immune function decreased in the acute stage,mainly manifested in the decrease of serum total T lymphocytes,CD4~+T lymphocytes and CD4~+/CD8~+,and the degree of decrease was positively correlated with the severity of the disease;2.The levels of serum pro-inflammatory and anti-inflammatory cytokines in patients with large area cerebral infarction in anterior circulation were increased in the acute stage,mainly in the increase of pro-inflammatory cytokines;3.CD4~+/CD8~+is an independent risk factor for 28 day death in patients with massive anterior circulation cerebral infarction.When CD4~+/CD8~+is less than 1.235,the risk of death increases.更多还原