轻型颅脑损伤伴轻度认知功能障碍患者血清HMGB1和TLR2及TLR4水平及其临床意义研究

Levels of HMGB1,TLR2 and TLR4 in Serum and Their Clinical Significance in Patients with Mild Traumatic Brain Injury Combined with Mild Cognitive Impairment

背景颅脑损伤后常导致不同程度的认知功能障碍,其发病率达20%～50%,严重影响生活质量,但其发病机制尚不清楚,基础研究相对匮乏。高迁移率族蛋白B1(HMGB1)是促炎因子,作用于Toll样受体(TLR)2、TLR4,激活核因子κB(NF-κB),其异常表达与认知功能障碍相关。目前关于颅脑损伤后继发认知功能障碍患者血清HMGB1、TLR2、TLR4水平的研究鲜有报道。目的观察轻型颅脑损伤(mTBI)伴轻度认知功能障碍(MCI)患者血清HMGB1、TLR2、TLR4水平及其临床意义。方法本研究为前瞻性研究,选取2016年6月—2017年12月郑州大学第五附属医院神经外科收治的符合纳入标准的格拉斯哥昏迷评分量表(GCS)评分为13～14分的m TBI患者75例为mTBI组(其中GCS评分14分38例,GCS评分13分37例;不伴MCI 53例,伴MCI 22例);选取同期在郑州大学第五附属医院门诊体检的健康者20例为健康组。采集研究对象清晨空腹外周静脉血并检测血清HMGB1、TLR2、TLR4水平。比较两组血清HMGB1、TLR2、TLR4水平,分析mTBI组中不同GCS评分、伴或不伴MCI患者血清HMGB1、TLR2、TLR4水平,以及mTBI伴MCI患者血清HMGB1、TLR2、TLR4水平间的相关性。结果 mTBI组血清HMGB1、TLR2、TLR4水平高于健康组(P<0.05)。mTBI组中GCS评分14分患者与GCS评分13分患者血清HMGB1、TLR2、TLR4水平比较,差异无统计学意义(P>0.05)。mTBI组中伴MCI患者血清HMGB1、TLR2、TLR4水平高于不伴MCI患者(P<0.05)。mTBI伴MCI患者血清HMGB1水平与血清TLR2、TLR4水平呈正相关[Y=0.438X-0.858(r=0.615,P=0.014);Y=0.494X+0.158(r=0.846,P<0.001)];mTBI伴MCI患者血清TLR2水平与血清TLR4水平无直线相关关系[Y=0.687X-0.178(r=0.372,P=0.055)]。结论 mTBI伴MCI的患者血清HMGB1、TLR2、TLR4水平较高,且高表达的HMGB1、TLR2、TLR4可能参与mTBI患者MCI的发生发展。

Background Traumatic brain injury(TBI)often leads to cognitive impairment in varying degrees.The morbidity is 20%-50%,which seriously affects the quality of life.However,its pathogenesis is still unclear and basic research is relatively scarce.High-mobility group box-1(HMGB1)is a proinflammatory factor,which acts on Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)to activate nuclear factor kappa B(NF-κB),and its abnormal expression is associated with cognitive impairment.The expression of serum HMGB1,TLR2 and TLR4 in patients with cognitive impairment after TBI has rarely been reported.Objective To detect the serum HMGB1,TLR2 and TLR4 levels of patients with mild traumatic brain injury(mTBI)combined with mild cognitive impairment(MCI)and analyze their clinical significance.Methods In this prospective study,seventy-five patients whose mTBI scored 13 to 14 in Glasgow Coma Scale(GCS)admitted to Department of Neurosurgery,the Fifth Affiliated Hospital of Zhengzhou University from June 2016 to December 2017 were determined as mTBI group(GCS scored 14 had 38 cases,GCS scored 13 had 37 cases,including 53 cases without MCI and 22 cases with MCI),meanwhile 20 normal subjects as control group were enrolled in this prospective study.Fasting peripheral venous blood was collected in the morning to detect the levels of HMGB1,TLR2,TLR4 in serum.The serum levels of HMGB1,TLR2 and TLR4 were compared between the two groups.The serum levels of HMGB1,TLR2 and TLR4 between GCS scored 13 and GCS scored 14 patients were analyzed.The serum levels of HMGB1,TLR2 and TLR4 between patients with MCI and patients without MCI were also analyzed.The correlations of HMGB1,TLR2 and TLR4 in serum of patients with mTBI combined with MCI were analyzed.Results Levels of HMGB1,TLR2 and TLR4 in serum in mTBI group were significantly higher than those in control group(P<0.05).There was no significant difference in serum levels of HMGB1,TLR2 and TLR4 between patients with GCS scored 14 and those with GCS scored 13 in mTBI group(P >0.05).HMGB1,TLR2 and TLR4 levels in serum of patients with mTBI combined with MCI were significantly higher than those in patients with mTBI without MCI(P<0.05).Levels of TLR2 and TLR4 in serum of patients with mTBI combined with MCI were both positively correlated with HMGB1 level〔Y=0.438X-0.858(r=0.615,P=0.014);Y=0.494X+0.158(r=0.846,P<0.001)〕,and the level of TLR2 was not correlated with TLR4 in patients with mTBI combined with MCI〔Y=0.687X-0.178(r=0.372,P=0.055)〕.Conclusion The serum levels of HMGB1,TLR2 and TLR4 were higher in patients with mTBI combined with MCI,and the high serum expression levels of HMGB1,TLR2 and TLR4 might be related to the occurrence and development of MCI in mTBI patients.