【摘要】： 最近幾場局部戰(zhàn)爭表明，隨著作戰(zhàn)樣式和戰(zhàn)術思想的轉(zhuǎn)變，各種爆炸性武器如精確制導炸彈、導彈、地雷等的應用日益廣泛，從而在大大提高武器打擊精確度和毀損力的同時，也明顯增加了肢體爆炸傷的發(fā)生率，使其達到了占傷員總數(shù)的40~70％，這不僅嚴重影響了部隊的戰(zhàn)斗力，也使現(xiàn)代火器傷的早期救治更為困難和復雜。眾所周知，現(xiàn)代爆炸傷傷情遠較一般火器傷嚴重，加之現(xiàn)代戰(zhàn)爭中部隊面臨的自然環(huán)境、軍事環(huán)境極為復雜，一些傷口根本無法在傷后6~8h內(nèi)得到及時的早期處理。因此，探討抗菌抗炎藥在肢體爆炸性傷口中的早期應用方法以延遲外科處理時間極為必要。 本實驗利用兔肢體爆炸傷模型，通過觀察傷后機體的全身狀況（體溫、呼吸及心率），傷道局部組織病理變化、局部組織的生化（TNF-a、IL-6）、氧分壓、細菌數(shù)量及組織壓力變化，了解肢體爆炸傷的傷情特點、炎癥反應及繼發(fā)損傷程度；在此基礎上，根據(jù)傷道區(qū)細菌學特點，分別選用環(huán)丙沙星、雙氯芬酸鈉作為抗菌、抗炎藥物，甲殼素(Chitin)、卡波姆(Carbomer)作為藥物緩釋的骨架材料，利用直接壓片的方法制得抗菌抗炎藥物緩釋片，并局部應用于傷道；然后利用高效液相色譜法等技術，測定了藥物在體外的溶出度和在傷區(qū)組織與血漿中的藥物濃度，觀察了藥物在體內(nèi)外的抑菌效果；最后將肢體爆炸傷動物分為對照組、清創(chuàng)組和用藥組，并于傷后2h、6h、12h、24h、36h，，分別觀察傷區(qū)組織病理，TNF-a、IL-6、SOD的含量，組織氧分壓，傷道組織細菌數(shù)量，壞死組織清除量及體溫、呼吸、心率等指標的變化。 實驗結果表明，在36h內(nèi)抗菌抗炎藥物緩釋片可向傷區(qū)穩(wěn)定釋放兩種藥物，環(huán)丙沙星在傷道組織中的濃度在最低抑菌濃度（MIC）以上（0.5ug/ml），且具有明顯的殺菌或抑菌作用；抗炎藥物雙氯芬酸鈉局部使用副作用小，能降低組織壓力，減少炎癥介質(zhì)（TNF-a、IL-6）的釋放，增加SOD活性，減少炎性細胞的局部侵潤以及組織繼發(fā)性壞死，從而在肢體爆炸傷后減輕組織過度炎癥反應中具有重要作用；藥物在血漿中的濃度較低，甚至不能測得，可在一定程度上減少局部用藥導致的副作用。所制備的藥物緩釋片，其藥物及骨架材料配伍合理，緩釋性能良好，可在體外和傷道周圍組織中持續(xù)穩(wěn)定釋放；應用于肢體爆炸傷口中，可延遲感染發(fā)生，降低組織內(nèi)壓力，減少炎癥介質(zhì)釋放，減輕組織繼發(fā)損傷，增加組織活力，改善機體全身狀況；且具有使用方便、操作簡單等特點；其對戰(zhàn)時或平時特定環(huán)境下爆炸傷的救治具有一定的實用參考價值。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2003
【分類號】：R826

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