【作者】 生学明；

【导师】 刘青蕊； 郭力；

【作者基本信息】 河北医科大学 ， 神经病学， 2003， 硕士

【摘要】 目的：脑囊虫病是一种我国常见的神经系统寄生虫疾病，占囊虫病的60%～80%，严重地危害人类的健康。脑囊虫病是一种变态反应性疾病，囊尾蚴在脑组织内有自身的生存规律，病理分期为生存期、退变死亡期（早期、后期）、钙化期（静止期）。脑囊虫病患者急性期是指囊虫退变死亡期，即从囊虫被破坏开始，到完全死亡为止。脑囊虫病患者的临床表现复杂多变，以头痛、癫痫、精神症状为主，主要取决于虫体寄生的位置、范围、数量，囊尾蚴的生活状态，周围组织反应的程度，血液循环及脑脊液循环障碍的程度，其中以癫痫为首发或继发症状者占67.5%。癫痫发生的病理生理机制复杂，癫痫的发作与囊虫寄生的部位有关，也与囊虫变性、死亡释放大量毒素、蛋白引起机体变态反应产生脑水肿有关。脑囊虫病造成脑细胞损伤的主要原因是由于免疫炎症反应导致代谢性酸中毒、细胞内钙超载、兴奋性氨基酸毒性反应、磷脂代谢障碍和自由基损伤、细胞因子作用等。一氧化氮（nitric oxide, NO）是一种信使物质，一种自由基。脑囊虫病患者急性期虫体破坏、代谢产物释放、异体蛋白释放，与产生的细胞因子共同刺激诱导巨噬细胞（Macrophage, M）激活诱导型一氧化氮合酶（iNOS）合成大量NO，一方面，有免疫保护作用、杀伤虫体、使之退变死亡；另一方面，<WP=4>脑组织出现免疫病理损伤，损害正常的组织结构，表现出临床方面的症状。关于NO抗微生物和寄生虫的作用机制至今尚未完全阐明，多数学者认为NO通过不同的途径发挥其抑制和杀伤微生物和寄生虫的作用。NO参与癫痫的发作已得到公认，但具体机制不明，目前存在两种说法，一是NO具有致痫作用、二是NO具有抗痫作用。本实验旨在探讨NO是否参与了脑囊虫病患者急性期痫性发作。 “活性氧”学说广泛地涉及生物体组织的病理生理过程，神经系统由于具有较高的氧代谢率、含有高密度的膜不饱和脂肪酸及信号传导依赖于完整的神经原突触联系，所以容易遭受活性氧中介物介导的损伤。生物机体在进化过程中产生了酶性和非酶性抗氧化系统，超氧化物歧化酶(super oxide dismutase, SOD)是存在于体内的自由基清除酶。SOD是一种金属蛋白酶，是体内非常重要的自由基清除剂之一，它可使自由基转为过氧化氢，再与谷胱甘肽氧化酶反应生成水，活性氧可能参与了SOD基因表达的调控。脑囊虫病患者精神症状、智能障碍可能与海马结构SOD的表达及调控有关，由于脑水肿、高颅压所致机械性损伤及大量自由基的产生，SOD在不同部位分布不同，分布于CA1区的CuZnSOD很快减少，分布于CA3区的MnSOD能持续较长时间，因此CA1区锥体细胞易受损而CA3区锥体细胞免于损伤。丙二醛(malondiall- dehyde, MDA)是脂质过氧化物代谢终产物，间接反映体内自由基损伤引起的脂质过氧化反应的程度。NO与SOD、MDA在脑囊虫病的发生、发展中发挥复杂的作用，研究表明，它们参与了脑囊虫病的炎症反应及免疫调节机制。本实验<WP=5>通过测定脑囊虫病患者急性期脑脊液中NO、SOD、MDA的水平，旨在探讨脑囊虫病的病理生理机制，为脑囊虫病患者的治疗提供一定的依据。方法：选择符合1985年全国脑囊虫病会议确定的诊断标准，不合并其它系统疾病，急性期但尚未经系统抗囊虫治疗的病人40例，其中男性22例、女性18例，平均年龄29.4±2.1岁，作为研究组。以囊虫试验阴性、脑脊液常规生化及细胞学检查无异常和影像学检查正常的9例头痛患者作为对照组。以研究组病人有无痫性发作分为癫痫组与非癫痫组各为27例与13例。所有的脑脊液标本保存于—70℃冰箱中待测。研究采用比色法，NO、SOD、MDA定量测定试剂盒（南京建成生物工程研究所产品），所有标本一次检测完成，以避免批间差异并设阳性与阴性对照。计量指标以均数±标准差表示，数据分析用SPSS 10.0统计软件计算均数和标准差，同时进行正态检验及方差齐性检验，多组间比较用单因素方差分析，当方差分析有显著性差异时，进一步做q检验进行两两比较，并对三项观察变量做多元相关分析。检验水准取a=0.05。结果： 1. 脑囊虫病患者急性期脑脊液中NO的均值24.6±2.3umol/L、MDA的均值31.5±3.4umol/L非常显著高于头痛患者脑脊液中NO的均值 14.5±1.5umol/L、MDA的均值20.5±2.2umol/L，有统计学上的意义(P<0.01)；脑囊虫病患者急性期脑脊液中SOD的均值3.1±0.3umol/L显著低于头痛患者脑脊液中SOD的均值10.6±1.1umol/L，有统计学上的意义(P<0.01)。2. 脑囊虫病患者急性期癫痫组脑脊液中NO的均值26.3±3.3umol/L，非<WP=6>癫痫组脑脊液中NO的均值21.3±2.5umol/L，两者比较均值有显著性差异（P<0.05）。3. 脑囊虫病患者癫痫组脑脊液中SOD的均值2.6±0.2umol/L略低于非癫痫组脑脊液中SOD的均值4.1±0.3umol/L；脑囊虫病患者癫痫组脑脊液中MDA的均值33.1±3.5umol/L略高于非癫痫组脑脊液中MDA的均值29.5±2.5umol/L，均无统计学上的意义(P>0.05)。4. 脑囊虫病患者急性期脑脊液中NO与MDA正相关(r=0.872，P<0.01)，与SOD负相关 (r=0.785，P<0.01)，MDA与SOD负相关（r=0.667，P<0.01）。结论：囊尾蚴感染是复杂的病理生理现象，脑囊虫病患者脑脊液中NO水平的升高，一方面，杀伤囊尾蚴的同时，更多还原

【Abstract】 Purpose：Cerebral cysticercosis is a common but severe central nervous system parasitic disease caused by encystment of the larvae of taenia solium, and in China it has 60%~80% incidence in the all cysticercosis cases. Cysticercosis belongs to an allergic disease.The larvae of taenia solium has its regular living pattern in brain tissue and which leads to different pathological processes. According to the pathological changes, it is divided into three stages: alive stage, the degeno-death stage (early and late stage) and the calcification (static) stage. The acute stage of cerebral cysticercosis is the degeno-death stage that is from larvae deterioration to their death. The clinical mannifestations of patients with cerebral cysticercosis are complicated and varied. The major symptoms include seizures、headache and mental disorders.The clinical symptoms are mainly related to the site, scope and number of cysticerci, to the living condition of the larvae of taenia solium, to the extent of tissue inflammation, and to the disfunction of blood and cerebrospinal fluid circulation. Epilepsy presents in up to 67.5% of cases. The pathophysiology mechanism that<WP=9>induces seizures is very complicated. Epilepsy is related not only to the location where cysticerci lie but also to the extent of brain edema. The edema is concerned with body allergy caused by the large quantity of toxin and protein released from denatured and dead cysticercus. The main methanism that leads to neuron injury is the immuno-inflammatory reaction which causes metabolic acidosis, intracelluar calcium ion (Ca2+) overload,exicitating amino acid (EAA) toxicity,lipoid metabolic disorder and free radicals mediating cell death, cytokine inducing neuron damage, etc. In the patients with cerebral cysticercosis in acute phage macrophage is activated due to the cysticercus’ denaturation and death which leads to some metabolites and protein releasing. Thus the activated macrophage secretes inducible nitric oxide synthetase (iNOS) and a large quantity of Nitric oxide (NO) is produced. It is not completely known about the mechanism of NO anti-parasite. It has been suggested that NO may inhibite the cysticercus’living and help to kill parasite by different means. NO is a highly reactive signal molecule. In one hand, it acts as an immune modulator and makes parasite deteriorate; in the other hand, it could damage brain tissue to display many clinical mannifestations. It has been widely accepted that NO is involved in the phathophysiology of seizures, but definite mechanism is not known. At present, there are two kinds of argument: one is that NO can induce seizures, the other is that NO is<WP=10>anti-epileptic. The aim of our study is to assess whether NO is invovled in seizures in patients with cerebral cysticercosis in acute stage. The active oxygen theroy is widely invovled in a diversity of pathophysiological processes in the body. Central nervous system is easily damaged by active oxygen because of its high oxygen metabolism, high density of non-saturated fatty acid and integrated synaptic circuit. As a sort of metal proteinase super oxide dismutase (SOD) is a major defensive factor against free radicals. SOD can make free radical change into H2O2 and H2O2 is changed into H2O by glutathine peroxidase. Active oxygen may be involved in the regulating expression of SOD mRNA. Mental and intelligence obstacles may be related to the conditions of expression and regulation of SOD mRNA in hippocampus regions. The brain edema and the large quantity of free radicals make CuZnSOD decrease quickly in field CA1 while MnSOD in CA3 maintains high density for a long time. So cone cells in field CA1 are more easily damaged than that in field CA3. Malondialldehyde (MDA) is the final metabolism product of lipoid peroxidation and it can indirectly show the extent of oxygen radical mediating lipoidic super-oxidated. NO, SOD and MDA are complicatedly involved in the immunopathophysiology mechanism of cerebral cysticercosis. The aim of this study is to provi更多还原