本文選題：創(chuàng)傷性顱腦損傷　切入點：基質(zhì)金屬蛋白酶　出處：《河北大學(xué)》2013年碩士論文

【摘要】：目的：創(chuàng)傷性顱腦損傷（Traumatic brain injury）在西方國家早就引起人們的注意，，它的致死和致殘的非常高[1]。改革開放以后這些年，我國的經(jīng)濟的如火箭升天般一樣直速上升，汽車的普遍，高速公路的提速等，我國顱腦傷發(fā)生率和因顱腦傷致死致殘的傷員也逐年增加。因此越來越多的學(xué)者開始關(guān)注并研究它。創(chuàng)傷性顱腦損傷遺留的偏癱，智力障礙等重大殘疾,給社會和家庭帶來沉重負擔，腦損傷后的直接結(jié)果是形成腦水腫,隨著腦水腫的進行性加重,顱內(nèi)壓增高,常導(dǎo)致腦病而死亡,且死亡率非常高，隨著相關(guān)研究的進一步深入,認識到腦損傷中血腦屏障(BBB)的損害在腦水腫的形成中起十分明顯的作用,而血腦屏障損害的實質(zhì)是一種膜系統(tǒng)受損的結(jié)果,對血腦屏障的超微結(jié)構(gòu)研究發(fā)現(xiàn),BBB由三層結(jié)構(gòu)組成:腦毛細血管內(nèi)皮細胞及其緊密連接而形成的基膜和膠質(zhì)細胞足突，腦損傷再灌注的損害亦表現(xiàn)為這三種結(jié)構(gòu)的破壞,從而改變其通透性致腦水腫的發(fā)生，基質(zhì)金屬蛋白酶(MMPS)是一個比較大的蛋白酶家族,主要分解細胞外基質(zhì)(ECM),機體同時存在金屬蛋白酶的組織抑制物(TIMPS),MMPS與TIMPS之間保持相對的特異性和功能上的動態(tài)平衡，在各種病理條件下打破了這種平衡,就會導(dǎo)致過分的細胞外基質(zhì)分解,產(chǎn)生相應(yīng)的病理損害。 因此通過檢測并分析腦外傷后的患者腦脊液及血液中MMP-9、MMP-2、TIMP-1及TIMP-2的表達與正常對照組中它們的表達的差異性，從而來探討TBI患者的腦脊液及血液中MMP-9、MMP-2、TIMP-1及TIMP-2的表達水平與TBI患者的的嚴重程度以及臨床預(yù)后等之間的關(guān)系。 方法：收集2012年1月～2012年10月期間河北大學(xué)附屬醫(yī)院神經(jīng)外科診斷為ＴＢＩ患者30例,30例患者按（Glasgow≤8分為重度組，8分的為輕度組）分為兩組，全部TBI患者于發(fā)病24小時內(nèi)入院,分別留取24h,72h和120h之內(nèi)腦脊液及靜脈血，30例ＴＢＩ患者測定MMP-9、MMP-2、TIMP-1及TIMP-2，對照組于采集時分別留取靜脈血及腦脊液各5ml左右,血液標本（腦脊液標本中為血性腦脊液的）靜置30分鐘使血液凝集，其余標本可直接檢驗,室溫1000Xg離心１０分鐘,吸取上清液(血清),立即置于-70℃，冰箱保存待測，ＴＢＩ患者分別分為觀察組輕重兩組,同時選取10例對照組（標本為檢驗科贈送,腦脊液標本為排除內(nèi)科顱內(nèi)疾病時篩選的正常腦脊液，均經(jīng)檢測為正常，血液標本為健康體檢時所采集的標本）,所有采集標本用雙抗體夾心ELISA法檢測觀察因子。 結(jié)果：本實驗檢測到MMP-9在TBI患者組腦脊液中24小時內(nèi)達到高峰，最少可以持續(xù)72小時，統(tǒng)計學(xué)顯示，24小時內(nèi)與72小時內(nèi)無顯著性差別，但是與120小時內(nèi)的檢測有顯著性差別。TIMP-1在120小時內(nèi)可達高峰，相對第72小時內(nèi)，第24小時內(nèi)有顯著性差異。MMP-2及TIMP-2在TBI患者的腦脊液中120小時內(nèi)無明顯變化。在血液中各檢測因子隨時間無明顯變化，TBI患者與對照組的MMP-9、MMP-2、TIMP-1及TIMP-2無論CST還是血液中的表達都有顯著性差異.重度TBI患者組的MMP-9在腦脊液水平顯著高于輕度TBI患者組。然而MMP-2、TIMP-1及TIMP-2在腦脊液中的表達在重度與輕度組之間無顯著性差異。在血液標本檢測中MMP-9、MMP-2、TIMP-1及TIMP-2的表達在重度與輕度組之間無顯著性差異。對所有的TBI患者組受傷后MMP-9（120小時）含量與TIMP-1（120小時）含量進行簡單相關(guān)性分析，結(jié)果顯示，兩者之間有直線相關(guān)關(guān)系，呈負相關(guān)，相關(guān)系數(shù)-0.593（P0.01），MMP-2與TIMP-2之間在各檢測點保持相關(guān)性。 結(jié)論：本課題在TBI不同分級患者及正常腦組織中檢測并分析了MMP-9、MMP-2、TIMP-1及TIMP-2的表達水平。研究發(fā)現(xiàn)如下： 1.TBI患者與對照組的MMP-9、MMP-2、TIMP-1及TIMP-2無論腦脊液還是血液中的表達都有顯著性差異。MMP-9在TBI患者組腦脊液中24小時內(nèi)達到高峰，最少可以持續(xù)72小時。對TBI患者來說，MMP-9的主要來源可能是神經(jīng)細胞。 2.MMP-9（120小時）含量與TIMP-1（120小時）在腦脊液中表達的含量進行簡單相關(guān)性分析，兩者變化趨勢相反。TIMP-1可能抑制MMP-9。 3.MMP-2與TIMP-2之間在在腦脊液中的表達于各檢測點保持負相關(guān)性，兩者變化趨勢相反。TIMP-2可能特異性抑制MMP-2。 4.TIMP-1可能是內(nèi)生源性保護因子。 5.MMP-9可以作為預(yù)測臨床預(yù)后的指標。
[Abstract]:Objective: traumatic brain injury (Traumatic brain injury) in western countries have long attracted attention after its morbidity and mortality is very high [1]. these years of reform and opening up, China's economy such as the rocket like speed straight rise, the common highway speed, our brain injury the incidence of death and disability due to brain injury and the wounded also increased year by year. Therefore, more and more scholars begin to pay attention to and study it. Traumatic brain injury left hemiplegia, mental retardation and other major disability, bring heavy burden to society and family, a direct result of brain damage is the formation of brain edema, with progressive cerebral edema, increased intracranial pressure, often lead to encephalopathy and death, and the mortality rate is very high, with further research, recognizing the brain damage of blood brain barrier (BBB) damage on edema formation in the very Obviously, the essence of BBB damage is the result of a damaged membrane system, ultrastructural study on blood brain barrier, BBB is composed of three layers: basement membrane and glial cell processes of brain capillary endothelial cells and tight junctions, brain injury and reperfusion injury also show that three kinds of structural damage, so as to change the permeability of brain edema caused by the occurrence of matrix metalloproteinase (MMPS) is a large protein family. The main decomposition of extracellular matrix (ECM), and the body of tissue inhibitor of metalloproteinases (TIMPS), keep the dynamic balance of specificity and relative function between the MMPS and TIMPS broke this balance in a variety of pathological conditions, will lead to excessive extracellular matrix decomposition, produce corresponding pathological damages.
Therefore, through the detection and analysis of blood and cerebrospinal fluid in patients with MMP-9 after traumatic brain injury in MMP-2, the differences of their expression of expression of TIMP-1 and TIMP-2 and the normal control group, so as to explore the MMP-9, blood and cerebrospinal fluid of patients with TBI in MMP-2, the relationship between the severity of the expression level of TIMP-1 and TIMP-2 in patients with TBI. And the clinical prognosis.
Methods: from January 2012 to October 2012 for the diagnosis of the Department of neurosurgery in the Affiliated Hospital of Hebei University during the period of 30 TBI patients, 30 patients (according to Glasgow is less than or equal to 8 divided into severe group, 8 were mild group) were divided into two groups, all TBI patients within 24 hours of admission were collected within 24h, 72h and 120h in cerebrospinal fluid and venous blood were measured in 30 patients with MMP-9, patients with TBI MMP-2, TIMP-1 and TIMP-2 in the control group were collected venous blood and cerebrospinal fluid of all blood samples (about 5ml in cerebrospinal fluid for bloody cerebrospinal fluid) and set aside for 30 minutes to make blood clots, the remaining samples can be tested directly, 1000Xg at room temperature and centrifuged for 10 minutes draw, supernatant (serum), immediately at -70 DEG C, refrigerator tested, TBI patients were divided into observation group two weight group, and 10 cases of control group (specimens for laboratory presentation of cerebrospinal fluid samples to exclude intracranial disease medicine Normal cerebrospinal fluid screened during disease was normal, and blood samples were collected by physical examination. All samples were detected by double antibody sandwich ELISA.
Results: the detection of MMP-9 reached the peak at 24 hours in TBI patients in the cerebrospinal fluid, at least for 72 hours, according to statistics, 24 hours and 72 hours had no significant difference, but the detection and within 120 hours there was a significant difference between the.TIMP-1 is within 120 hours of peak, the relative within seventy-second hours. Within twenty-fourth hours there was significant difference between.MMP-2 and TIMP-2 in cerebrospinal fluid in patients with TBI within 120 hours. No significant changes in the blood of each detection factor has no obvious change over time, MMP-2 TBI patients and control group MMP-9, TIMP-1, TIMP-2 and CST are both expression in the blood of the severe TBI were significantly different. A group of patients with MMP-9 in cerebrospinal fluid of patients with mild TBI group were significantly higher than that of MMP-2. However, the expression of TIMP-1 and TIMP-2 in cerebrospinal fluid in severe and mild group had no significant difference between MMP-2. MMP-9 in blood samples, TIMP-1 And the expression of TIMP-2 in severe and mild group had no significant difference between the group of patients with TBI. All of the injured after MMP-9 (120 hours) and the content of TIMP-1 (120 hours) were simple correlation analysis, results show that there is a linear correlation between negative correlation, correlation coefficient -0.593 (P0.01), MMP-2 with TIMP-2 in the detection and remain relevant.
Conclusion: the level of expression of MMP-9, MMP-2, TIMP-1 and TIMP-2 was detected and analyzed in different grades of TBI and normal brain tissue.
MMP-2 1.TBI patients and control group, MMP-9, TIMP-1 and TIMP-2 both in the blood or cerebrospinal fluid expression had significant differences in.MMP-9 reached the peak at 24 hours in TBI patients in the cerebrospinal fluid, at least lasts 72 hours. For patients with TBI, the main source of MMP-9 may be the nerve cells.
There was a simple correlation between 2.MMP-9 (120 hours) content and TIMP-1 (120 hours) expression in CSF. The difference between them is opposite..TIMP-1 may inhibit MMP-9..
The expression of 3.MMP-2 and TIMP-2 in the cerebrospinal fluid is negatively correlated with each detection point, and the change trend is contrary to.TIMP-2, which may inhibit MMP-2. specifically.
4.TIMP-1 may be an endogenous protective factor.
5.MMP-9 can be used as a predictor of clinical prognosis.

【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R651.15

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