缓释抗菌抗炎药在兔肢体软组织爆炸伤早期处理中的作用

发布时间：2018-11-26 12:16

【摘要】： 最近几场局部战争表明，随着作战样式和战术思想的转变，各种爆炸性武器如精确制导炸弹、导弹、地雷等的应用日益广泛，从而在大大提高武器打击精确度和毁损力的同时，也明显增加了肢体爆炸伤的发生率，使其达到了占伤员总数的40~70％，这不仅严重影响了部队的战斗力，也使现代火器伤的早期救治更为困难和复杂。众所周知，现代爆炸伤伤情远较一般火器伤严重，加之现代战争中部队面临的自然环境、军事环境极为复杂，一些伤口根本无法在伤后6~8h内得到及时的早期处理。因此，探讨抗菌抗炎药在肢体爆炸性伤口中的早期应用方法以延迟外科处理时间极为必要。本实验利用兔肢体爆炸伤模型，通过观察伤后机体的全身状况（体温、呼吸及心率），伤道局部组织病理变化、局部组织的生化（TNF-a、IL-6）、氧分压、细菌数量及组织压力变化，了解肢体爆炸伤的伤情特点、炎症反应及继发损伤程度；在此基础上，根据伤道区细菌学特点，分别选用环丙沙星、双氯芬酸钠作为抗菌、抗炎药物，甲壳素(Chitin)、卡波姆(Carbomer)作为药物缓释的骨架材料，利用直接压片的方法制得抗菌抗炎药物缓释片，并局部应用于伤道；然后利用高效液相色谱法等技术，测定了药物在体外的溶出度和在伤区组织与血浆中的药物浓度，观察了药物在体内外的抑菌效果；最后将肢体爆炸伤动物分为对照组、清创组和用药组，并于伤后2h、6h、12h、24h、36h，，分别观察伤区组织病理，TNF-a、IL-6、SOD的含量，组织氧分压，伤道组织细菌数量，坏死组织清除量及体温、呼吸、心率等指标的变化。实验结果表明，在36h内抗菌抗炎药物缓释片可向伤区稳定释放两种药物，环丙沙星在伤道组织中的浓度在最低抑菌浓度（MIC）以上（0.5ug/ml），且具有明显的杀菌或抑菌作用；抗炎药物双氯芬酸钠局部使用副作用小，能降低组织压力，减少炎症介质（TNF-a、IL-6）的释放，增加SOD活性，减少炎性细胞的局部侵润以及组织继发性坏死，从而在肢体爆炸伤后减轻组织过度炎症反应中具有重要作用；药物在血浆中的浓度较低，甚至不能测得，可在一定程度上减少局部用药导致的副作用。所制备的药物缓释片，其药物及骨架材料配伍合理，缓释性能良好，可在体外和伤道周围组织中持续稳定释放；应用于肢体爆炸伤口中，可延迟感染发生，降低组织内压力，减少炎症介质释放，减轻组织继发损伤，增加组织活力，改善机体全身状况；且具有使用方便、操作简单等特点；其对战时或平时特定环境下爆炸伤的救治具有一定的实用参考价值。
[Abstract]:Recent local wars have shown that with the change in operational style and tactical thinking, various explosive weapons, such as precision-guided bombs, missiles, mines, etc., are increasingly being used, thus greatly improving the precision and destructive force of weapons. It also increases the incidence of limb explosive injury and makes it reach 40700.This not only seriously affects the combat effectiveness of troops, but also makes the early treatment of modern firearm injuries more difficult and complicated. As we all know, the modern explosive injury is far more serious than the general firearm injury. In addition, the military environment is extremely complex because of the natural environment faced by the troops in the modern war. Some wounds can not be treated early in time within 6 minutes and 8 hours after the injury. Therefore, it is necessary to explore the early application of antimicrobial and anti-inflammatory drugs in limb explosive wounds in order to delay the time of surgical treatment. In this experiment, the animal model of limb explosive injury was used to observe the whole body condition (body temperature, respiration and heart rate), the pathological changes of local tissue, the biochemical (TNF-a,IL-6) of local tissue and the partial pressure of oxygen. The number of bacteria and the change of tissue pressure were studied to understand the injury characteristics, inflammatory reaction and secondary injury degree of limb explosion injury. On this basis, ciprofloxacin and diclofenac sodium were selected as antimicrobial and anti-inflammatory drugs according to the bacteriological characteristics of the wound tract area, and chitin (Chitin), carbomer (Carbomer) was used as the framework material for drug sustained release. The antibacterial and anti-inflammatory drug sustained release tablets were prepared by the method of direct pressing tablets, and were used locally in the injured tract. Then the dissolution in vitro and the concentration in tissue and plasma were determined by high performance liquid chromatography (HPLC), and the bacteriostatic effect of drugs in vivo and in vitro was observed. The animals were divided into three groups: control group, debridement group and medication group. The tissue pathology, the content of TNF-a,IL-6,SOD, the partial pressure of oxygen, the number of bacteria in the wound tract were observed at 2 h after injury, and the tissue pathology, the content of TNF-a,IL-6,SOD, the tissue oxygen pressure and the number of bacteria in the wound tract were observed. Changes of necrotic tissue clearance and body temperature, respiration, heart rate, etc. The results showed that the sustained-release tablets could release two kinds of drugs stably into the injured area within 36 hours. The concentration of ciprofloxacin in the injured tissue was above the minimum inhibitory concentration (MIC) (0.5ug/ml). And has obvious bactericidal or bacteriostatic effect; The local use of diclofenac sodium can reduce tissue pressure, reduce the release of inflammatory mediators (TNF-a,IL-6), increase the activity of SOD, reduce the local infiltration of inflammatory cells and secondary necrosis of tissues. Therefore, it plays an important role in reducing the excessive inflammation of the tissues after the limb explosion injury. Low or even undetectable concentrations of drugs in plasma can reduce the side effects of local drug use to some extent. The prepared drug sustained-release tablets have reasonable compatibility and good sustained-release properties, and can be released steadily in vitro and in the tissues around the wound tract. It can delay infection, reduce the pressure in the tissue, reduce the release of inflammatory mediators, reduce the secondary injury of the tissue, increase the vitality of the tissue, improve the whole body condition, and have the characteristics of convenient use and simple operation. It has certain practical reference value for the treatment of explosive injury in wartime or peacetime.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2003
【分类号】：R826

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