自然杀伤细胞在创伤性脑损伤中的变化研究

发布时间：2018-05-16 14:54

本文选题：自然杀伤细胞 + 创伤性脑损伤　；参考：《天津医科大学》2014年博士论文

【摘要】：研究目的：通过测定创伤性脑损伤(Traumatic Brain Injury,TBI)患者外周血中自然杀伤(Natural Killer cells, NK cells)细胞表型的变化,探讨伤后不同时间NK细胞水平与不同程度TBI的关系。研究内容： TBI是导致我国青壮年死亡的主要原因之一,有极高的致死率和伤残率,构成重大的公共卫生和社会经济问题。新研究发现神经损伤的程度似乎与固有免疫活动规模和活性程度相关,细胞和体液免疫系统在TBI的损伤机制中起到的关键作用。NK细胞是与T、B细胞并列的第三类群淋巴细胞,是免疫监视的第一道防线,可以调控适应性免疫的发生,具有极强的免疫学调节功能。本研究以不同程度TBI患者外周血中NK细胞变化为研究内容,为进一步探讨脑损伤与免疫反应的关系,探明TBI的发病机制,为探寻新的TBI治疗方式提供参考。研究方法：选择30例于天津医科大学总医院神经创伤监护中心收治的闭合性颅脑外伤患者,根据格拉斯哥昏迷评分(Glasgow Coma Scale, GCS)评定脑损伤程度,选择轻、中、重不同程度TBI患者各10例。分别于脑损伤后1、3、7、14、21天采集外周血样,应用流式细胞仪检测方法分析外周血CD3-CD56+NK细胞百分比和绝对值数量变化。同步收集性别,年龄等一般临床资料与TBI患者相对照的20例正常健康志愿者外周血标本。统计不同程度TBI患者感染类型、感染率,测定中重TBI患者清晨血清皮质醇浓度,随访伤后3和6个月格拉斯哥预后评分(Glasgow Outcome Scale,GOS)评价神经功能预后,进一步探讨伤后不同时间NK细胞与GCS、GOS评分关系,明确感染与NK细胞变化的关系,初步探讨TBI后固有免疫变化机制。研究结果： 1、与健康对照组相比,轻度TBI患者NK细胞的百分比和绝对值数量在伤后第1天和第3天呈显著下降,伤后7天,NK细胞的百分比和绝对值数量恢复至正常范围水平；中度TBI患者相同的时间点的CD3-CD56+NK细胞的百分比和绝对值数量的变化趋势并不完全相同,伤后7天,NK细胞的百分比和绝对值数量与对照组比较均明显降低,外周血NK细胞的绝对值数量于伤后21天已恢复正常范围；重度TBI患者外周血中最低NK细胞百分比和绝对值数量被发现在伤后3-7天,此外,NK细胞百分比和绝对值数量在伤后21天仍没有恢复正常水平。 2、TBI患者感染发生率较高,最常见的感染并发症为肺部感染、尿路感染和败血症。感染组与非感染组TBI患者在伤后3-7天左右出现NK细胞的统计学差异,感染组NK细胞相对非感染组呈显著下降趋势。 3、TBI组患者伤后7、14和21天NK细胞与GCS评分呈正相关：伤后3、6个月,TBI后7、14天NK细胞与GOS评分呈正相关；感染组和非感染组TBI组患者伤后7天NK细胞与GCS评分呈正相关；感染组外周血NK细胞百分比和绝对值数量和3、6个月的GOS评分无明显相关；非感染组在伤后7天外周血NK细胞和GOS评分相关性有统计学意义。研究结论： 1、本研究调查了不同程度TBI患者外周血中NK细胞百分比和绝对值数量的变化。结果提示脑损伤后伴随着外周血中NK细胞的比例和数目的减少,脑损伤愈严重,NK细胞减少愈明显,呈先下降后缓慢复原的趋势。研究揭示了创伤性脑损伤可以诱发外周血NK细胞的减少。 2、脑损伤后常伴有严重的颅外全身系统并发症,原因与免疫失衡和中枢神经系统诱发的免疫缺陷相关。常见并发症为严重的肺部感染、尿路感染和败血症等。我们发现不同程度TBI患者罹患颅外感染的几率不同,在TBI疾病发展过程中,外周血固有免疫反应的主要效应细胞—NK细胞发生了戏剧性的变化,其变化趋势与感染发生规律有相关性。 3、NK细胞可能在某种程度上对TBI患者的神经功能和预后产生一定影响。严重TBI后常伴随下丘脑-垂体-肾上腺轴功能衰竭及中枢性免疫抑制的发生,我们选定中重度TBI患者检测清晨外周血清皮质醇浓度,进一步探讨TBI患者合并外周血NK细胞减少的机制。改善中枢神经损伤后NK细胞功能可能会对控制感染和改善预后起到帮助,但同时避免NK细胞对自体细胞的识别和过度对获得性免疫的调控也是进一步思考的课题。总之,TBI诱导NK细胞病理变化原因可能是复杂和多方面的,尚需进一步的探索和研究。
[Abstract]:The purpose of the study is:
The changes in the natural killer (Natural Killer cells, NK cells) cell phenotype in peripheral blood of patients with traumatic brain injury (Traumatic Brain Injury, TBI) were measured to explore the relationship between NK cell level and TBI in different degrees after injury.
Research content:
TBI is one of the main causes of the death of young and middle-aged people in China, with high mortality and disability rates, which constitute major public health and socioeconomic problems. The new study finds that the degree of nerve damage seems to be related to the scale and activity of inherent immunity, and the key role of cell and humoral immune system in the damage mechanism of TBI. .NK cells are third groups of lymphocytes which are parallel to T and B cells. It is the first line of defense for immune surveillance. It can regulate the occurrence of adaptive immunity and has a very strong immunological function. This study took the changes of NK cells in peripheral blood of different degree TBI patients as the research content, and further explored the relationship between brain damage and immune response. The pathogenesis of Ming TBI provides a reference for exploring new TBI treatment modalities.
Research methods:
30 cases of closed craniocerebral trauma treated in the nerve trauma center of General Hospital Affiliated to Tianjin Medical University were selected to evaluate the degree of brain injury according to the Glasgow Coma Scale (Glasgow Coma Scale, GCS). 10 cases of TBI were selected light, medium and heavy, and the peripheral blood samples were collected on 1,3,7,14,21 days after brain injury, and flow cytometry was applied. The percentage and absolute value of CD3-CD56+NK cells in peripheral blood were analyzed by means of instrument detection. The peripheral blood samples of 20 normal healthy volunteers, such as sex, age, and other TBI patients, were collected synchronously. The infection type, infection rate of different degree TBI patients, the early morning serum cortisol concentration in the middle TBI patients were measured, and the follow-up was followed up. Glasgow prognosis score (Glasgow Outcome Scale, GOS) was evaluated at 3 and 6 months after injury. The relationship between NK cells and GCS, GOS score at different time after injury was further explored, and the relationship between infection and NK cell changes was clearly defined. The mechanism of intrinsic immune change after TBI was preliminarily discussed.
The results of the study:
1, compared with the healthy control group, the percentage and absolute value of NK cells in the mild TBI patients decreased significantly at the first and third days after injury, and the percentage and absolute value of NK cells recovered to the normal level at 7 days after injury, and the change trend of the percentage and absolute value of CD3-CD56+ NK cells at the same time point for moderate TBI patients The percentage and absolute value of NK cells in the 7 days after injury were significantly lower than those in the control group, and the absolute value of NK cells in peripheral blood recovered to the normal range on the 21 day after injury, and the percentage and absolute value of the lowest NK cells in the peripheral blood of severe TBI patients were 3-7 days after the injury, in addition, the percentage of NK cells and the absolute number of cells were in great extent. The number of values did not return to normal level on the 21 day after injury.
2, the incidence of infection in TBI patients was higher. The most common infection complications were pulmonary infection, urinary tract infection and septicemia. The TBI patients in the infection group and non infected group had statistical differences in the NK cells about 3-7 days after the injury, and the NK cells in the infected group decreased significantly compared with the non infected group.
3, in group TBI, the 7,14 and 21 day NK cells were positively correlated with the GCS score: 3,6 months after injury, NK cells in 7,14 days after TBI were positively correlated with GOS score, and NK cells were positively correlated with GCS scores at 7 days after injury in the infection group and non infected group, and there was no obvious percentage and absolute value of peripheral blood cells in the infection group. The correlation between NK cells and GOS scores in the non infected group was statistically significant on the 7 day after injury.
The conclusions are as follows:
1, this study investigated the changes in the percentage and absolute value of NK cells in peripheral blood of TBI patients. The results suggest that after brain injury, the more the proportion and the number of NK cells in the peripheral blood, the more serious the brain damage, the more obvious the decrease of the NK cells, and the trend of the decrease of the number of cells. The study reveals that traumatic brain injury can be found. The decrease of NK cells in peripheral blood was induced.
2, after brain injury, severe systemic systemic complications are often associated with severe immune disorders and immune deficiency induced by central nervous system. The common complications are severe pulmonary infection, urinary tract infection and septicemia. We found different degrees of TBI patients with different levels of extracranial infection, in the course of the development of TBI disease, and in the peripheral The main effector cells of blood innate immune response, NK cells, have changed dramatically, and the trend of changes is related to the regularity of infection.
3, NK cells may have some influence on the neurological function and prognosis of TBI patients. Severe TBI often accompanied by hypothalamus pituitary adrenal failure and central immune suppression. We selected moderate and severe TBI patients to detect the concentration of serum cortisol in early morning peripheral blood, and further explore the NK fine in peripheral blood of TBI patients. NK cell function may be helpful to control infection and improve prognosis after the improvement of central nerve injury, but it is also a subject for further thinking to avoid the identification of autologous cells by NK cells and the regulation of excessive immunity to acquired immunity. In a word, the cause of TBI induced pathological changes of NK cells may be complex and multifaceted. Further exploration and research are still needed.

【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R651.15

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