本文選題：自然殺傷細(xì)胞 + 創(chuàng)傷性腦損傷�。� 參考：《天津醫(yī)科大學(xué)》2014年博士論文

【摘要】：研究目的： 通過(guò)測(cè)定創(chuàng)傷性腦損傷(Traumatic Brain Injury,TBI)患者外周血中自然殺傷(Natural Killer cells, NK cells)細(xì)胞表型的變化,探討傷后不同時(shí)間NK細(xì)胞水平與不同程度TBI的關(guān)系。 研究?jī)?nèi)容： TBI是導(dǎo)致我國(guó)青壯年死亡的主要原因之一,有極高的致死率和傷殘率,構(gòu)成重大的公共衛(wèi)生和社會(huì)經(jīng)濟(jì)問(wèn)題。新研究發(fā)現(xiàn)神經(jīng)損傷的程度似乎與固有免疫活動(dòng)規(guī)模和活性程度相關(guān),細(xì)胞和體液免疫系統(tǒng)在TBI的損傷機(jī)制中起到的關(guān)鍵作用。NK細(xì)胞是與T、B細(xì)胞并列的第三類群淋巴細(xì)胞,是免疫監(jiān)視的第一道防線,可以調(diào)控適應(yīng)性免疫的發(fā)生,具有極強(qiáng)的免疫學(xué)調(diào)節(jié)功能。本研究以不同程度TBI患者外周血中NK細(xì)胞變化為研究?jī)?nèi)容,為進(jìn)一步探討腦損傷與免疫反應(yīng)的關(guān)系,探明TBI的發(fā)病機(jī)制,為探尋新的TBI治療方式提供參考。 研究方法： 選擇30例于天津醫(yī)科大學(xué)總醫(yī)院神經(jīng)創(chuàng)傷監(jiān)護(hù)中心收治的閉合性顱腦外傷患者,根據(jù)格拉斯哥昏迷評(píng)分(Glasgow Coma Scale, GCS)評(píng)定腦損傷程度,選擇輕、中、重不同程度TBI患者各10例。分別于腦損傷后1、3、7、14、21天采集外周血樣,應(yīng)用流式細(xì)胞儀檢測(cè)方法分析外周血CD3-CD56+NK細(xì)胞百分比和絕對(duì)值數(shù)量變化。同步收集性別,年齡等一般臨床資料與TBI患者相對(duì)照的20例正常健康志愿者外周血標(biāo)本。統(tǒng)計(jì)不同程度TBI患者感染類型、感染率,測(cè)定中重TBI患者清晨血清皮質(zhì)醇濃度,隨訪傷后3和6個(gè)月格拉斯哥預(yù)后評(píng)分(Glasgow Outcome Scale,GOS)評(píng)價(jià)神經(jīng)功能預(yù)后,進(jìn)一步探討傷后不同時(shí)間NK細(xì)胞與GCS、GOS評(píng)分關(guān)系,明確感染與NK細(xì)胞變化的關(guān)系,初步探討TBI后固有免疫變化機(jī)制。 研究結(jié)果： 1、與健康對(duì)照組相比,輕度TBI患者NK細(xì)胞的百分比和絕對(duì)值數(shù)量在傷后第1天和第3天呈顯著下降,傷后7天,NK細(xì)胞的百分比和絕對(duì)值數(shù)量恢復(fù)至正常范圍水平；中度TBI患者相同的時(shí)間點(diǎn)的CD3-CD56+NK細(xì)胞的百分比和絕對(duì)值數(shù)量的變化趨勢(shì)并不完全相同,傷后7天,NK細(xì)胞的百分比和絕對(duì)值數(shù)量與對(duì)照組比較均明顯降低,外周血NK細(xì)胞的絕對(duì)值數(shù)量于傷后21天已恢復(fù)正常范圍；重度TBI患者外周血中最低NK細(xì)胞百分比和絕對(duì)值數(shù)量被發(fā)現(xiàn)在傷后3-7天,此外,NK細(xì)胞百分比和絕對(duì)值數(shù)量在傷后21天仍沒(méi)有恢復(fù)正常水平。 2、TBI患者感染發(fā)生率較高,最常見(jiàn)的感染并發(fā)癥為肺部感染、尿路感染和敗血癥。感染組與非感染組TBI患者在傷后3-7天左右出現(xiàn)NK細(xì)胞的統(tǒng)計(jì)學(xué)差異,感染組NK細(xì)胞相對(duì)非感染組呈顯著下降趨勢(shì)。 3、TBI組患者傷后7、14和21天NK細(xì)胞與GCS評(píng)分呈正相關(guān)：傷后3、6個(gè)月,TBI后7、14天NK細(xì)胞與GOS評(píng)分呈正相關(guān)；感染組和非感染組TBI組患者傷后7天NK細(xì)胞與GCS評(píng)分呈正相關(guān)；感染組外周血NK細(xì)胞百分比和絕對(duì)值數(shù)量和3、6個(gè)月的GOS評(píng)分無(wú)明顯相關(guān)；非感染組在傷后7天外周血NK細(xì)胞和GOS評(píng)分相關(guān)性有統(tǒng)計(jì)學(xué)意義。 研究結(jié)論： 1、本研究調(diào)查了不同程度TBI患者外周血中NK細(xì)胞百分比和絕對(duì)值數(shù)量的變化。結(jié)果提示腦損傷后伴隨著外周血中NK細(xì)胞的比例和數(shù)目的減少,腦損傷愈嚴(yán)重,NK細(xì)胞減少愈明顯,呈先下降后緩慢復(fù)原的趨勢(shì)。研究揭示了創(chuàng)傷性腦損傷可以誘發(fā)外周血NK細(xì)胞的減少。 2、腦損傷后常伴有嚴(yán)重的顱外全身系統(tǒng)并發(fā)癥,原因與免疫失衡和中樞神經(jīng)系統(tǒng)誘發(fā)的免疫缺陷相關(guān)。常見(jiàn)并發(fā)癥為嚴(yán)重的肺部感染、尿路感染和敗血癥等。我們發(fā)現(xiàn)不同程度TBI患者罹患顱外感染的幾率不同,在TBI疾病發(fā)展過(guò)程中,外周血固有免疫反應(yīng)的主要效應(yīng)細(xì)胞—NK細(xì)胞發(fā)生了戲劇性的變化,其變化趨勢(shì)與感染發(fā)生規(guī)律有相關(guān)性。 3、NK細(xì)胞可能在某種程度上對(duì)TBI患者的神經(jīng)功能和預(yù)后產(chǎn)生一定影響。嚴(yán)重TBI后常伴隨下丘腦-垂體-腎上腺軸功能衰竭及中樞性免疫抑制的發(fā)生,我們選定中重度TBI患者檢測(cè)清晨外周血清皮質(zhì)醇濃度,進(jìn)一步探討TBI患者合并外周血NK細(xì)胞減少的機(jī)制。改善中樞神經(jīng)損傷后NK細(xì)胞功能可能會(huì)對(duì)控制感染和改善預(yù)后起到幫助,但同時(shí)避免NK細(xì)胞對(duì)自體細(xì)胞的識(shí)別和過(guò)度對(duì)獲得性免疫的調(diào)控也是進(jìn)一步思考的課題�？傊�,TBI誘導(dǎo)NK細(xì)胞病理變化原因可能是復(fù)雜和多方面的,尚需進(jìn)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.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R651.15

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本文編號(hào)：1897310