摘要
第一部分颅脑创伤后神经内分泌改变研究
目的:观察中重型男性颅脑创伤(Traumatic brain injury,TBI)患者伤后血清神经内分泌激素、炎症标志物变化。
材料与方法:选取我院颅脑创伤救治中心收治的GCS评分12分以下男性患者48例(排除内分泌疾病史),分别于伤后第1、3、7、14、21天采取静脉血,收集血清置于-80℃冰箱保存,统一应用全自动化学发光仪进行PGN、COR、T3、T4、E2、TES、EPO、FSH、GH、INS、LH、PRL、TSH、IL-2R、IL-6的检测。以正常范围作为参照,将各个时间点的各种检测指标进行分类,计算高于正常范围、正常范围、低于正常范围的发生率,以图表显示;分别对各个分组、分层的数据群进行计算,以中位数表示,用图表加以显示比较。
结果:在本组患者的15项内分泌和免疫指标的检测中,所有患者至少在其中一个时间点存在至少一项的检测指标异常,上述指标发生至少一项异常改变的发生率100%;各种检测指标不同时间点异常发生率,同一指标高于或低于正常范围的中位数如图表(图5～38)所示。中、重型颅脑创伤男性患者内分泌、免疫发生改变的机率较高,其中甲状腺功能类激素多表现降低后逐步向正常范围恢复;促黄体生成激素可高可低,但多数异常者表现为增高;泌乳素表现异常者主要是增高;雌二醇异常者表现为伤后增高;孕酮异常者主要表现一过性增高;胰岛素变化不明显;生长激素异常者存在明显的增高;促红细胞生成素异常者存在明显增高;皮质醇异常者主要表现为增高,但也有少数患者皮质醇不升反降;雄激素异常者存在明显降低;炎症标志物明显增高。
结论:颅脑创伤后神经内分泌发生改变的机率高,结合免疫改变,进行相关治疗将促进患者恢复。
第二部分免疫抑制与颅脑创伤后抗脑抗体相关性的研究
目的:通过动物实验证实颅脑创伤后机体产生抗脑抗体;免疫抑制剂、亚低温治疗能够减少此类抗体产生。
材料和方法:18只成年新西兰大白兔(雌雄不限)。随机分为A、B、C三组,每组6只,三组均开7mm直径颅骨窗后予以液压打击,其中,A组—亚低温治疗;B组—免疫抑制剂治疗;C组—对照组,打击后不予任何处理,正常饲养。三组兔均于伤后0d、3d、7d、14d、21d、28d时间点耳缘静脉取血4ml,分离血清,置-20℃保存。收齐标本后用酶联免疫吸附试验(enzyme linked immunosorbentassay,ELISA)检测抗脑抗体的动态变化。除此之外,在以上各时间点抽取耳缘静脉血2ml,抗凝,测定外周血白细胞计数。
结果:三组大白兔在未遭受打击之前,体内均有少量抗脑抗体的存在;在予以单侧液压打击后,三组大白兔血清中均有抗脑抗体峰值的出现,亚低温组和免疫抑制剂组大白兔体内抗脑抗体峰值的出现较对照组推迟,而且其峰值也比对照组低;三组大白兔血清中抗脑抗体浓度值经统计学处理后发现:亚低温组和免疫抑制剂组分别与对照组相比较,均有显著性差异(P＜0.05)。三组大白兔在打击后,亚低温组和免疫抑制剂组其血液中自细胞计数均比对照组要低,说明这两组大白兔在给予亚低温和免疫抑制治疗后,其机体免疫功能下降。三组大白兔外周血中自细胞计数经统计学处理后发现,亚低温组和免疫抑制剂组分别与对照组相比较,均有显著性差异(P＜0.05)。
结论:1.在正常状态下,血清中可能存在少量抗脑抗体;2.颅脑创伤后,血清中抗脑抗体与正常状态相比将有所升高;3.颅脑创伤后体内升高的抗脑抗体可能会攻击自身脑组织,所以通过本实验我们提出颅脑创伤可能具有自身免疫性疾病的特点;4.颅脑创伤后,亚低温、免疫抑制治疗通过降低机体免疫力,均可以降低自身抗脑抗体的产生,减轻其对脑组织的攻击作用。5.通过本实验我们提出,免疫抑制治疗将可能是一种新的颅脑创伤治疗方法。
Part 1:Study on neuroendocrine changing of post-TBI
Objective:To observe the change of the patient's neuroendocrine hormone and inflammative marker in serum after medium and severe TBI.
Methods:48 patients were selected from the traumatic center of our hospital and their GCS were all under 12(without endocrine disease).They were phlebotomized 1d 3d 7d 14d 21d after injury and we preserved their serum in refrigerator under 80 degrees below zero after centrifugalization.PGN,COR,T3,T4, E2,TES,EPO,FSH,GH,INS,LH,PRL,TSH,IL-2R,IL-6were detected by the automate chemiluminescence machine.According to the reference ranges,the indexes detected at different times can be classified and with calculation we got the rate which may be higher,lower than the normal level or in the reference ranges demonstrated by the diagram.We calculated the data of every group with median using statistic methods and compared with diagrams.
Results:In the 15 kinds of endocrine- and immune- indexes,at least one index was abnormal at one time point of all the patients.We demonstrated this consequence with table5-38.The rate of the change which occured at the male patient's endocrine hormones and immune functions after medium and severe TBI was high.The levels of T3,T4 mostly decreased at first,then restored to the normal level;LH may be high or low,mostly showed to increase;PRL and E2 demonstrated to increase;PGN increased only for a short time;INS had no obvious change;GH and EPO increased obviously;COR mainly increased,but at a few circumstance it may decreased;TES decreased obviously;IL-2R and IL-6 increased obviously.
Conclusions:The rate of the neuroendocrine and immune changes which occurred after TBI is high and it will accelerate the recovery of the patients after taking the related therapies.
Part 2:A Study of the relationship between immunosuppression and antibrain-antibody(ABAb)after traumatic brain injury
Objective:To establish an animal model to prove the production of ABAb after TBI;also mild hypothermia therapy and immunosuppression therapy can decrease the ABAb.
Methods:18 adult New Zealand white rabbits(no matter male or female)were divided into 3 groups,every group had 6 rabbits,all 3 groups were trephined of 7mm diameter cranial hole and fluid percussion applied.Group A—mild hypothermia therapy group;Group B—immunosuppression therapy group;Group C—control group,treated with nothing after fluid percussion,fed normally.All three groups of rabbits were phlebotomized 4ml blood through the ear fringe vein 0d、3d、7d、14d、21d、28d after injury.The blood serum must be centrifuged and then conserved with -20℃.These specimens were tested by ELISA,observed the dynamic change of Antibrain-antibody(ABAb).Except that,2ml blood phlebotomized through the ear fringe vein must be anticoagulated in order to counting the number of the white blood cell.
Results:A low level of ABAb had been found in the blood serum of all the rabbits before bitted;After LFPI,every group had its respective peak value of the ABAb.The peak value of group A、B appeared later and lower than group C.There was statistically significant difference between group A and C,group B and C(P＜0.05).After LFPI,the number of the WBC of groups A and B was fewer than group C which showed that after mild hypothermia and imrnunosuppression therapy,the immune function of groups A、B had been decreased.There was statistically significant difference between A and C group,B and C group(P＜0.05).
Conclusions:1.In nature state,there was a low level of ABAb in the blood serum of all the rabbits;2.After traumatic brain injury,the concentration of ABAb was higher than nature state;3.After traumatic brain injury,the increased ABAb would likely to attack self brain tissues,so that we considered that traumatic brain injury could have the characters just like autoimmune diseases;4.After traumatic brain injury,mild hypothermia and immunosuppression therapies could decrease the concentration of ABAb by repressing the immune functions;5.The experiment proved that immunosuppression therapy will become a new methode dealling with traumatic brain injury.
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