摘要
研究背景：全氟碳化合物是血液代用品中的一种，携氧能力高、具有排泄二氧化碳能力、无毒、不含血液有形成份的人工合成的化合物。1966年Clark等证明氟碳乳剂具有携氧能力。美、日、法、德等国家对氟碳进行了研究，取得了进展。1972年2月，日本大柳等进行了正常人体实验，1979年日本和美国先后进行氟碳临床实验。但在此研究及应用过程中，基础研究明显不够，氟碳的有效性及安全性需要进一步得到实验验证；在重度失血性休克过程中，脑组织极易受到缺血缺氧的损害，氟碳在纠正失血休克过程中对脑组织的保护作用，尚无实验有效证实。这是本实验研究的主要目的所在。
本实验采用上海博纳科技发展有限公司生产的新型第二代携氧型纳米化全氟碳化合物-全氟溴烷，采用特种光源进行光化反应进行合成，并选用特定的催化剂及高效精制技术进行分离提纯，将副产物与未反应完的原料除净，纯度高达99.5％；采用先进的纳米技术制备制剂，得到平均粒径为100纳米左右、分布均匀的稳定乳液。其具有良好的化学稳定性和热稳定性。全氟碳化合物具有载氧和扩充血容量的作用，其携氧能力40-50ml％，约为水的20倍，血液的2倍。在酸碱性溶液中均不被破坏，加热也不发生变化。本制剂可在常温下稳定贮存，并可高温高压灭菌，为以前的氟碳化合物所不具备的特性。
目的：通过建立新西兰兔失血性休克模型，观察评价纳米化全氟碳比合物的抗失血性休克作用及其有效性和安全性，及对脑皮质神经元的保护作用。
方法：雄性新西兰大白兔20只，体重2Kg左右，随机分成二组，实
纳米化全氟碳化合物在失血休克中神经保护作用的实验研究 军医进修学院
验组10只，应用氟碳化合物，对照组10只，应用羟乙基淀粉代血浆。
解剖出左侧股动脉及右侧股静脉，分别用套管针穿刺股动脉及股静脉，
股动脉插管测压、放血和作动脉血气测定，股静脉插管作为输液用。全
身肝素化门 八g）后测股动脉压，抽取股动脉血测定 PH、PO。及K；等
血气分析值。然后股动脉开始放血，在15分钟左右的时间内使动脉压下
降到40mmHg，并维持60分钟，完成失血性休克模型。再次抽取动脉血
测定血气分析值。此时所有动物开始面罩吸氧，实验组动物用与失血等
量的氟碳化合物自股静脉快速回输，对照组则输与失血等量的羟乙基淀
粉代血浆（约30分钟左右输完）。面罩吸氧氧浓度为60％，氧流量为ZL／
分。吸氧条件下监测2小时，重复测定上述各项指标。术毕，同等条件
下饲养观察12小时生存率。对每个标本，以相同的顶叶皮质部位，进行
电镜观察超微结构，并连续切片 10张，H．E染色，每张切片在 200倍视
野下观察。作为该标本进行统计分析的正常或损伤损伤神经元数的相对
数据。
结果：12小时存活率实验组比对照组高。实验组心率与对照组无明
显差异。实验组呼吸较对照组深大，次数加快。实验组动物在监测结束
时血压平均为80上8．gmmHg，较对照组为高。实验组动脉血氧分压较对照
组明显升高。两组间动脉血二氧化碳分压有明显差别，实验组CO。排泄
较对照组增强。对照组血气有明显变酸趋势。实验组动物瞳孔监测结束
时较对照组偏小，瞳孔对光反射较灵敏。组织学观察可见光镜下切片可
见实验组动物脑皮层损伤较对照组明显减轻，实验组动物皮层神经元细
胞形态基本正常，核仁清晰，对照组皮层神经元呈典型呈细胞肿胀，核
仁消失，中央型尼氏小体溶解等各种改变。实验组损伤神经元数目与对
照组比较有统计学显著性差异。电镜下可见对照组神经元呈核染色质稀
疏，核膜不清，线粒体、核糖体肿胀，线粒体峭消失，核糖体聚集，胞
二
纳米化全氟碳化合物在失血休克中神经保护作用的实验研究 军医进修学院
浆结构紊乱或消失，实验组无上述典型改变。
结论：本组新西兰兔失血性休克的实验研究，表明纳米化全氟碳化
合物具有明确抗失血性休克作用，且通过多方面的作用机制对脑皮质神
经元具有明显保护的功能。证明氟碳是一种有效安全的神经保护剂。在
临床应用前景中，可应用于脑缺血的神经保护。
Perfluorocarbon(PFC) is one of blood substitutes,and has the capability that carries high oxygen,exclude carbon dioxide.lt is man-made chemical compounding of nonpoisonous and non-blood elements in it.In 1966,Clark prove that Perfluorocarbon emulsion possesses carrying the oxygen ability.The researchs has been in progress to Perfluorocarbon in nations such as the U.S.A , Japan , France and Germany etc , and some progress have been gained.In 1972, Japan carried on the normal human body experiment, and the clinical experiment of PFC is carried on in Japan and U.S.A in 1979.But in this process of study and the application ,the fundamental research is clear inadequately , and the effectiveness and safety of PFC need to get the experiment certification further;in the course of heavier degree hemorrhagic shock, brain tissue damaged by short of the cerebral blood and short of oxygen supplying, and in the treatment to hemorrhagic shock of PFC, the protection effect to brain tissue is not effectively confirmed in experiment . This is the main propose of the experiment.
This experiment use the new second generation carrying oxygen and nanometer type PFC, and this type PFC is composed by using the special type light source to carry on the actinic reaction , and choosing specially designated catalyzer and high efficiency refinement technology to separate and purify , and the outgrowth and raw material that does not react except clean ,the purity degree 99.5%. Uses the nanometer
technology prepare the preparation , and gets the average granul diametre to control for 100 nanometers and even stable distributes latex. PFC possesses good chemistry stability and hot stability. This PFCcarries oxygen ability 40-50ml%, about serve as the water 20 times, 2 times of blood. All not being destroyed in the acid and alkalescence solution , the change does not also occur in the heating . This preparation can stablely be stored under normal temperature,and can be exterminated bacterium under the high temperature and high pressure, and the peculiarity is not possessed in old tyoe PFC.
Objective:Establish rabbits model to observe and view the function of effectiveness and safety of PFC in the course of treatment to hemorrhagic shock ,and the function of protecting cerebral cortex nerve cells.
Methods:A totle 20 Male New Zealand rabbits in 2 groups(each of the 2 groups consisting of 10 rabbits).All of rabbits are completed the modle of hemorrhagic shock .Experimental group used PFC and control group used 706 blood substitute.In the course of treatment,all of rabbits breath oxygen in veil.In the course of experiment,heart beat ,breath rate,blood pressure,artery vigour,pupil, light reflect,survival rate in 12hours are observed.To every sample,in the same parietal lobe cortex,with electron microscope and light microscope stucture is observed.Date were reported as mean + SD. Statistical significance levels
were calculated by using Analysis of t test and x test.
Results:In 12 hours survival rate in experimental group is higher than control group.The heart beat rate is not significantly different in both
group.Breath in experimental group is deeper than control group and berath rate is also faster.In experimental group,blood pressure and PaC>2 is significantly higher than it in control group. PaCC>2 in experimental group evacuate higher than central group.The control group has the trand of going acid.Pupil light reflect in experimental group is sensitiver than control group. From light microscrope the parietal lobe cortex in experimental group are damaged less than control group,the structure and shape are almost normal, nucleolus clear;the neuron in control group swell,nucleolus extinct,central Nissl body extinct.The number of damage neuron is significant different in both group. From electron microscope in control group nuclear chromatin in neuron is rare,nuclear membrane is not clear,mitochondria ribosome swell,mitochondrial crista extinct,ribosomal aggregate,structure in neuron disorder and extinct.There are not ab
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