亚低温治疗与颅脑创伤后β-淀粉样蛋白动态变化规律的相关性研究
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摘要
目的：正常人脑组织中β淀粉样蛋白(amyloidβpeptide,Aβ含量甚少,但在创伤后其含量可能会大幅度增高,本实验通过对创伤后脑脊液中β淀粉样蛋白的浓度变化,分析亚低温在临床治疗中的作用及和预后的关系,并通过建立常温和亚低温大鼠TBI模型,进一步确证亚低温治疗重型颅脑创伤与常规治疗相比是否具有一定的优势,进一步揭示亚低温的脑保护作用机制,为临床亚低温的应用提供理论依据。
方法：本课题分为二部份,第一部分：根据一定的标准,选取2009年10月～2010年8月入住武警医学院附属医院亚低温及神经外科重症监护病房(NICU)住院治疗的sTBI (GCS≤8分)患者共60例,随机分为亚低温组和对照组(常规治疗组),其中亚低温治疗组和对照组各30例,分别于术后第1、3、5、7天留取脑脊液,采用双抗体夹心酶联免疫吸附试验(ELISA)法测定脑脊液中Aβ蛋白含量,并监测期间ICP值及半年后GOS评分,第二部分试验选取健康雄性SD大鼠12只,随机分成正常组、对照组、颅脑创伤+常温组和颅脑创伤+低温治疗组,各组动物均为3只。制作大鼠液压冲击模型。低温组动物创伤后立即应用冰浴降温,维持脑温大约(32±2)℃,常温组只进行打击,不行低温,假手术组只行麻醉及开颅,不给予打击及低温干预,创伤后6小时断头取脑,运用免疫荧光及PCR检测脑组织Aβ含量。
结果：第一部分结果示：创伤后脑脊液中Aβ蛋白于术后第3天变化明显,而且Aβ升高明显的患者,其ICP值较高,GOS评分较低,预后较差,第二部分试验结果示：正常组及对照组Aβ含量无明显改变,创伤+常温组可见Aβ明显升高,颅脑创伤+低温组脑组织中Aβ明显较正常组升高明显,但升高幅度较创伤+常温组低。
结论：在常规治疗的同时,采用亚低温治疗可抑制重型颅脑创伤患者的Aβ的表达及ICP水平并提高患者预后,Aβ作为一种新生物标记物,其动态变化与颅脑创伤损伤程度有一定相关性,Aβ含量变化作为患者预后一项评定指标。
Objective:There is very few A(3 in normal brain tissue, but its content may be greatly increased after TBI, this study is to detect concentration changes of Aβin cerebrospinal fluid at different times after TBI, Evaluate the rlationship between the function of mild hypothermia in clinical treatment and prognosis, estabish stable normothermia and mild hypothermia rat fluid percusstion brain injury models, compared with conventional treatment, further confirmed mild hypothermia has advantages, and reveal the mechanism for brain protection in clinical, provides the theory basis for the further research.
Methods:The study includes two parts.Part one:sixty sTBI patients were random selected, All 60 patients who were hospitaled in the department of neurosurgery of the Affiliated Hospital of Chinese People's Armed Police Force from October 2009 to August 2010 with sTBI(GCS<8 points),which were randomly assigned into two groups,30 patients with mild hypothermia treatment (HT group), and 30 cases with routine treatment(NT group). Mild hypothermia was induced within 24 hours after TBI,and maintain the rectal temperature(RT) in (32-35)℃,The Aβconcentration level of CSF was measured by ELISA method at 1,3,5 and 7 day after TBI.Meantime, the intracranial pressure(ICP) were also measured and the prognosis was evaluated by Glasgow Outcome Scale after six months. The second part were selected 12 healthy, free diet feeding conditions SD rats. The adult male Sprague Dawley rats were randomly assigned to normal group(n=3), sham injury group(n= 3), TBI-mild hypothermia group (n=3) and TBI-normothermia group, The rats of TBI-mild hypothermia group received hypothermia intervention with ice-water bathing after TBI was induced though the lateral fluid percussion device. The brain temperature was adjusted to (32±2)℃and maintained for 6 h. The TBI-normothermia group underwent all surgical and anesthetic procedures except the hypothermia implement. The sham injury group underwent all surgical and anesthetic procedures except the TBI and hypothermia implement,the histopathological evaluation was performed with immune fluorescence staining and RT-PCR in three rats of every group at six hours post-TBI.
Results:The first parts sugested:Compared with mild hypothermia group,the Aβin cerebrospinal fluid is significantly increased after 3 days post-trauma, the ICP value is lower, GOS score higher with good prognosis, the second part showed:normal group and sham group have no changes in Ap,however TBI-NT group showed significantly higher than HT group.
Conclusion:TBI may induce some significant alternation of Aβ,while conventional treatment,take mild hypothermia in the patients with sTBI can lower ICP levels and improve the prognosis of patients, mild hypothermia could inhibit expressive change of Aβ,as a new biomarker, there is relationship between the dynamic changes and degree of TBI.
方法：本课题分为二部份,第一部分：根据一定的标准,选取2009年10月～2010年8月入住武警医学院附属医院亚低温及神经外科重症监护病房(NICU)住院治疗的sTBI (GCS≤8分)患者共60例,随机分为亚低温组和对照组(常规治疗组),其中亚低温治疗组和对照组各30例,分别于术后第1、3、5、7天留取脑脊液,采用双抗体夹心酶联免疫吸附试验(ELISA)法测定脑脊液中Aβ蛋白含量,并监测期间ICP值及半年后GOS评分,第二部分试验选取健康雄性SD大鼠12只,随机分成正常组、对照组、颅脑创伤+常温组和颅脑创伤+低温治疗组,各组动物均为3只。制作大鼠液压冲击模型。低温组动物创伤后立即应用冰浴降温,维持脑温大约(32±2)℃,常温组只进行打击,不行低温,假手术组只行麻醉及开颅,不给予打击及低温干预,创伤后6小时断头取脑,运用免疫荧光及PCR检测脑组织Aβ含量。
结果：第一部分结果示：创伤后脑脊液中Aβ蛋白于术后第3天变化明显,而且Aβ升高明显的患者,其ICP值较高,GOS评分较低,预后较差,第二部分试验结果示：正常组及对照组Aβ含量无明显改变,创伤+常温组可见Aβ明显升高,颅脑创伤+低温组脑组织中Aβ明显较正常组升高明显,但升高幅度较创伤+常温组低。
结论：在常规治疗的同时,采用亚低温治疗可抑制重型颅脑创伤患者的Aβ的表达及ICP水平并提高患者预后,Aβ作为一种新生物标记物,其动态变化与颅脑创伤损伤程度有一定相关性,Aβ含量变化作为患者预后一项评定指标。
Objective:There is very few A(3 in normal brain tissue, but its content may be greatly increased after TBI, this study is to detect concentration changes of Aβin cerebrospinal fluid at different times after TBI, Evaluate the rlationship between the function of mild hypothermia in clinical treatment and prognosis, estabish stable normothermia and mild hypothermia rat fluid percusstion brain injury models, compared with conventional treatment, further confirmed mild hypothermia has advantages, and reveal the mechanism for brain protection in clinical, provides the theory basis for the further research.
Methods:The study includes two parts.Part one:sixty sTBI patients were random selected, All 60 patients who were hospitaled in the department of neurosurgery of the Affiliated Hospital of Chinese People's Armed Police Force from October 2009 to August 2010 with sTBI(GCS<8 points),which were randomly assigned into two groups,30 patients with mild hypothermia treatment (HT group), and 30 cases with routine treatment(NT group). Mild hypothermia was induced within 24 hours after TBI,and maintain the rectal temperature(RT) in (32-35)℃,The Aβconcentration level of CSF was measured by ELISA method at 1,3,5 and 7 day after TBI.Meantime, the intracranial pressure(ICP) were also measured and the prognosis was evaluated by Glasgow Outcome Scale after six months. The second part were selected 12 healthy, free diet feeding conditions SD rats. The adult male Sprague Dawley rats were randomly assigned to normal group(n=3), sham injury group(n= 3), TBI-mild hypothermia group (n=3) and TBI-normothermia group, The rats of TBI-mild hypothermia group received hypothermia intervention with ice-water bathing after TBI was induced though the lateral fluid percussion device. The brain temperature was adjusted to (32±2)℃and maintained for 6 h. The TBI-normothermia group underwent all surgical and anesthetic procedures except the hypothermia implement. The sham injury group underwent all surgical and anesthetic procedures except the TBI and hypothermia implement,the histopathological evaluation was performed with immune fluorescence staining and RT-PCR in three rats of every group at six hours post-TBI.
Results:The first parts sugested:Compared with mild hypothermia group,the Aβin cerebrospinal fluid is significantly increased after 3 days post-trauma, the ICP value is lower, GOS score higher with good prognosis, the second part showed:normal group and sham group have no changes in Ap,however TBI-NT group showed significantly higher than HT group.
Conclusion:TBI may induce some significant alternation of Aβ,while conventional treatment,take mild hypothermia in the patients with sTBI can lower ICP levels and improve the prognosis of patients, mild hypothermia could inhibit expressive change of Aβ,as a new biomarker, there is relationship between the dynamic changes and degree of TBI.
引文
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