腦脊液Notch1、DLL1的檢測在中樞神經系統(tǒng)感染性疾病中的臨床價值
發(fā)布時間：2018-08-17 17:46
【摘要】：背景與目的 結核性腦膜炎(Tuberculous meningitis,TM)是臨床上常見的中樞神經系統(tǒng)感染性疾病之一,近年來發(fā)病率有增加的趨勢,正確的診斷、早期的治療是決定預后的重要因素。由于臨床抗生素的大范圍使用和腦膜炎臨床表現(xiàn)往往不典型而且復雜多變,細菌學檢驗因周期過長,加上敏感度低,病原菌檢出困難等,往往不利于早期診斷,容易誤診和漏診。 Notch信號屬于進化上保守的轉導通路,參與胚胎的發(fā)展和自我更新,以及調節(jié)細胞的命運,是生物發(fā)育中必不可少的途徑。而且,這條途徑涉及各信號之間復雜的相互作用,與許多疾病的病理生理過程相關。DLL1是Notch受體的配體之一,其功能缺失可能導致胚胎死亡,但DLL蛋白水平的變化,在疾病中的作用研究甚少。 我們前期的工作發(fā)現(xiàn),TM患者血清和腦脊液(Cerebrospinal Fluid, CSF)中DLL1水平顯著升高,具有較重要的診斷意義。在此基礎上,本研究將繼續(xù)采用酶聯(lián)免疫吸附試驗(Enzyme Linked Immunosorbent Assays, ELISA)和Western Blot的方法檢測中樞神經系統(tǒng)感染性疾病患者CSF中可溶性Notch1和DLL1的水平,探索新的TM的診斷方法。 對象和方法 選取鄭州大學第一附屬醫(yī)院神經內科2008年7月-2012年3月住院行腰椎穿刺術的患者289例,根據臨床診斷進行分組。其中TM組127例。非TM的感染性腦(膜)炎對照90例,包括化膿性腦膜炎組(Purulent meningitis,PM)10例,病毒性腦膜炎組(Viral meningitis,VM)65例,新型隱球菌性腦膜炎組(Cryptococcus neoformans meningitis, CM)15例。非感染性神經系統(tǒng)疾病對照組72例,選擇同期入住排除中樞神經系統(tǒng)感染的患者,包括吉蘭-巴雷綜合征(Guillain-Barre syndrome,GBS)20例,多發(fā)性硬化(Multiple sclerosis, MS)25例,阿爾茨海默病(Alzheimer disease, AD)8例,低顱壓頭痛10例,緊張性頭痛9例。本研究經鄭州大學第一附屬醫(yī)院醫(yī)學倫理委員會批準,患者均簽署知情同意書。采用ELISA和Western Blot的方法檢測各組CSF中可溶性Notch1、DLL1的含量和表達。 結果 1.各組腦脊液中可溶性Notch1的含量,TM組也明顯高于其余各組(P0.01)；以Notch1≥8.50pg/ml作為TM的判斷值,其敏感度為86.8%,特異性為85.2%,但是此標準對于隱球菌腦炎區(qū)分較差,其余各組之間相比均無顯著差異(P0.05)。 2.各組腦脊液中可溶性DLL1的含量,TM組顯著高于其余各組(P0.01)；以DLL1≥0.77ng/ml作為TM的判斷值,其敏感度為100%,特異性為96.9%,其余各組之間相比無明顯差異(P0.05)。 3.伴發(fā)高甘油三酯與否腦脊液可溶性Notch1、DLL1的含量測定結果：TM組伴高甘油三酯、TM組伴正常甘油三酯的CSF中Nocth1含量分別為(6.85±2.32,7.30±1.35pg/m1),兩者相比無顯著性差異(P0.05)；其余各組伴高甘油三酯或正常甘油三酯CSF中Nocth1含量相比也無顯著性差異(P0.05)。TM組伴高甘油三酯、TM組伴正常甘油三酯的CSF中DLL1含量分別為(3.18±2.92,3.62±1.79ng/ml),兩者相比無顯著性差異(P0.05)；其余各組伴高甘油三酯或正常甘油三酯CSF中Nocth1含量相比也無顯著性差異(P0.05)。 4. Western Blot結果提示,TM組患者腦脊液中Notch1、DLL-1蛋白有較高的表達,其余各組患者極少表達。 5.39例TM組患者隨訪結果發(fā)現(xiàn),37例有效化療治療4周后,CSF可溶性Notch1、DLL1水平顯著下降(5.78±2.87pg/ml,1.89±0.58ng/ml),兩者相比有顯著性差異(P0.05),治療12周可以降至正常水平(0.85±0.62pg/ml,2.05±1.21ng/ml),兩者相比有顯著性差異(P0.05)。2例治療效果不佳,CSF可溶性Notch1、DLL1水平未見下降。 結論 本研究提示,TM患者CSF中可溶性Notch1、DLL1的含量顯著升高,在VM、PM、隱球菌性腦膜炎和非感染性神經系統(tǒng)疾病患者的CSF中可溶性Notch1、DLL1的含量較低或檢測不到。因此,CSF中Notch1及其配體DLL1含量的檢測,有望成為診斷結核性腦膜炎的輔助指標。
[Abstract]:Background and purpose
Tuberculous meningitis (TM) is one of the common infectious diseases of the central nervous system in clinic. The incidence of TM is increasing in recent years. Correct diagnosis and early treatment are important factors for prognosis. Bacteriological examination is often not conducive to early diagnosis, easy to misdiagnose and miss diagnosis because of its long cycle, low sensitivity and difficult detection of pathogens.
Notch signaling is an evolutionarily conserved transduction pathway involved in embryonic development and self-renewal, as well as the regulation of cell fate, which is essential in biological development. Loss of energy may lead to embryonic death, but there is little research on the role of DLL protein level in disease.
Our previous work found that the levels of DLL1 in serum and cerebrospinal fluid (CSF) of TM patients were significantly elevated, which is of great diagnostic significance. On this basis, this study will continue to use Enzyme Linked Immunosorbent Assays (ELISA) and Western Blot methods to detect central nervous system infections. The levels of soluble Notch1 and DLL1 in CSF of patients with sexual diseases were explored, and a new diagnostic method for TM was explored.
Objects and methods
A total of 289 patients with lumbar puncture in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from July 2008 to March 2012 were selected and divided into two groups according to their clinical diagnosis, 127 patients in TM group and 90 patients in non-TM infectious meningitis control group, including 10 patients with purulent meningitis (PM) and 10 patients with viral meningitis (VM). 65 cases, 15 cases of Cryptococcus neoformans meningitis (CM), 72 cases of non-infectious nervous system disease control group, selected patients excluding central nervous system infection at the same time, including Guillain-Barre syndrome (GBS) 20 cases, multiple sclerosis (MS) 25 cases, Al This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University. The contents and expressions of soluble Notch1 and DLL1 in CSF were detected by ELISA and Western Blot.
Result
1. The content of soluble Notch1 in cerebrospinal fluid of each group was also significantly higher in TM group than in other groups (P 0.01); the sensitivity and specificity of TM were 86.8% and 85.2% respectively when Notch1 (>8.50pg/ml) was used as the judgment value of TM, but the standard was not well differentiated from cryptococcal encephalitis, and there was no significant difference among the other groups (P 0.05).
2. The content of soluble DLL1 in cerebrospinal fluid of each group was significantly higher in TM group than that in other groups (P 0.01); the sensitivity and specificity of TM were 100% and 96.9% respectively with DLL1 (>0.77 ng/ml), and there was no significant difference among the other groups (P 0.05).
3. Contents of soluble Notch1 and DLL 1 in cerebrospinal fluid with or without high triglycerides: The contents of Nocth1 in CSF with high triglycerides in TM group and normal triglycerides in TM group were (6.85 (+ 2.32), 7.30 (+ 1.35 pg/m1), respectively. There was no significant difference between the two groups (P 0.05). The content of DLL1 in CSF with high triglyceride in TM group and normal triglyceride in TM group was 3.18 (+ 2.92) and 3.62 (+ 1.79 ng/ml), respectively. There was no significant difference between the two groups (P 0.05). There was no significant difference in the content of Nocth1 in CSF with high triglyceride or normal triglyceride in other groups (P 0.05).
4. Western Blot results showed that the expression of Notch1 and DLL-1 protein in cerebrospinal fluid of TM group was higher than that of other groups.
The follow-up results of 5.39 TM patients showed that the levels of CSF soluble Notch 1 and DLL 1 decreased significantly (5.78 (+ 2.87 pg/ml) and 1.89 (+ 0.58 ng/ml) after 4 weeks of effective chemotherapy in 37 TM patients. There was significant difference between the two groups (P 0.05). After 12 weeks of treatment, the levels of CSF soluble Notch 1 and DLL 1 decreased to normal level (0.85 (+ 0.62 pg/ml) and 2.05 (+ 1.21 ng/ml). The CSF Notch1 and DLL1 levels did not decrease.
conclusion
This study suggests that the levels of soluble Notch1 and DLL1 in CSF of TM patients are significantly higher than those of VM, PM, cryptococcal meningitis and non-infectious nervous system diseases. The levels of soluble Notch1 and DLL1 in CSF of TM patients are lower or undetectable. Indicators.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R529.3
[Abstract]:Background and purpose
Tuberculous meningitis (TM) is one of the common infectious diseases of the central nervous system in clinic. The incidence of TM is increasing in recent years. Correct diagnosis and early treatment are important factors for prognosis. Bacteriological examination is often not conducive to early diagnosis, easy to misdiagnose and miss diagnosis because of its long cycle, low sensitivity and difficult detection of pathogens.
Notch signaling is an evolutionarily conserved transduction pathway involved in embryonic development and self-renewal, as well as the regulation of cell fate, which is essential in biological development. Loss of energy may lead to embryonic death, but there is little research on the role of DLL protein level in disease.
Our previous work found that the levels of DLL1 in serum and cerebrospinal fluid (CSF) of TM patients were significantly elevated, which is of great diagnostic significance. On this basis, this study will continue to use Enzyme Linked Immunosorbent Assays (ELISA) and Western Blot methods to detect central nervous system infections. The levels of soluble Notch1 and DLL1 in CSF of patients with sexual diseases were explored, and a new diagnostic method for TM was explored.
Objects and methods
A total of 289 patients with lumbar puncture in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from July 2008 to March 2012 were selected and divided into two groups according to their clinical diagnosis, 127 patients in TM group and 90 patients in non-TM infectious meningitis control group, including 10 patients with purulent meningitis (PM) and 10 patients with viral meningitis (VM). 65 cases, 15 cases of Cryptococcus neoformans meningitis (CM), 72 cases of non-infectious nervous system disease control group, selected patients excluding central nervous system infection at the same time, including Guillain-Barre syndrome (GBS) 20 cases, multiple sclerosis (MS) 25 cases, Al This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University. The contents and expressions of soluble Notch1 and DLL1 in CSF were detected by ELISA and Western Blot.
Result
1. The content of soluble Notch1 in cerebrospinal fluid of each group was also significantly higher in TM group than in other groups (P 0.01); the sensitivity and specificity of TM were 86.8% and 85.2% respectively when Notch1 (>8.50pg/ml) was used as the judgment value of TM, but the standard was not well differentiated from cryptococcal encephalitis, and there was no significant difference among the other groups (P 0.05).
2. The content of soluble DLL1 in cerebrospinal fluid of each group was significantly higher in TM group than that in other groups (P 0.01); the sensitivity and specificity of TM were 100% and 96.9% respectively with DLL1 (>0.77 ng/ml), and there was no significant difference among the other groups (P 0.05).
3. Contents of soluble Notch1 and DLL 1 in cerebrospinal fluid with or without high triglycerides: The contents of Nocth1 in CSF with high triglycerides in TM group and normal triglycerides in TM group were (6.85 (+ 2.32), 7.30 (+ 1.35 pg/m1), respectively. There was no significant difference between the two groups (P 0.05). The content of DLL1 in CSF with high triglyceride in TM group and normal triglyceride in TM group was 3.18 (+ 2.92) and 3.62 (+ 1.79 ng/ml), respectively. There was no significant difference between the two groups (P 0.05). There was no significant difference in the content of Nocth1 in CSF with high triglyceride or normal triglyceride in other groups (P 0.05).
4. Western Blot results showed that the expression of Notch1 and DLL-1 protein in cerebrospinal fluid of TM group was higher than that of other groups.
The follow-up results of 5.39 TM patients showed that the levels of CSF soluble Notch 1 and DLL 1 decreased significantly (5.78 (+ 2.87 pg/ml) and 1.89 (+ 0.58 ng/ml) after 4 weeks of effective chemotherapy in 37 TM patients. There was significant difference between the two groups (P 0.05). After 12 weeks of treatment, the levels of CSF soluble Notch 1 and DLL 1 decreased to normal level (0.85 (+ 0.62 pg/ml) and 2.05 (+ 1.21 ng/ml). The CSF Notch1 and DLL1 levels did not decrease.
conclusion
This study suggests that the levels of soluble Notch1 and DLL1 in CSF of TM patients are significantly higher than those of VM, PM, cryptococcal meningitis and non-infectious nervous system diseases. The levels of soluble Notch1 and DLL1 in CSF of TM patients are lower or undetectable. Indicators.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R529.3
【參考文獻】
相關期刊論文 前4條
1 李盡義;賈延R，
本文編號：2188408
本文鏈接：http://sikaile.net/yixuelunwen/chuanranbingxuelunwen/2188408.html
最近更新
教材專著
