摘要
目的建立胞壁酰二肽（MDP）诱发烫伤大鼠脓毒症模型。方法选择SPF级健康雄性SD大鼠50只，体重200～250g，2—3月龄，采用随机数字表法，将其分为3组：对照组（C组，n=10）、烫伤组（s组，n=10），制备20％总体表面积Ⅲ度烫伤模型；MDP组（n=30），于烫伤后24h时经股静脉注射MDP5mg／kg。MDP组于注射MDP后1、6、24h时，s组于烫伤后24h时，C组于20℃水中假烫伤后24h时取腹主动脉血样，分别行血气分析、计数WBC和Plt、检测肝肾功能、肌酸激酶同工酶（CK—MB）活性、血浆TNF-α、干扰素-γ（IFN-γ）、IL-6、IL-10、高迁移率族蛋白-1（HMGB-1）水平；取血样后处死大鼠，取心、肝、肺和肾组织行病理学检查，另取肺组织测定髓过氧化物酶（MPO）活性。另取雄性sD大鼠90只，按照上述方法分组处理后，记录72h生存情况。结果与C组比较，S组血浆IL-6、IL-10、IFN-γ和HMGB1水平、WBC计数、血清ALT、AST和BUN水平、肺组织MPO活性升高，生存率降低，MDP组血浆TNF-α、IL．6、IL-10、IFN-γ和HMGB-1水平、血清ALT、AST、总胆红素、BUN、Cr和CK-MB水平、肺组织MPO活性、PaCO2升高，BE负值增加，WBC和Plt计数、pH值、PaO2和生存率降低（P〈0．05）。与S组比较，MDP组血浆TNF-α、IL-6、IFN-γ和HMGB-1水平，血清ALT、AST、总胆红素、BUN、Cr、CK．MB水平、肺组织MPO活性和PaCO2升高，BE负值增加，WBC和Plt计数、pH值、PaO2和生存率降低（P〈0．05）。s组和MDP组心、肝、肺和肾组织病理学损伤明显，MDP组病理学损伤程度较重。结论Ⅲ度烫伤后经MDP诱导可致大鼠广泛炎性反应并伴多器官功能损伤，成功建立烫伤后脓毒症模型。
Objective To establish a rat model of sepsis induced by muramyl dipeptide （MDP） after scald burn.Methods Fifty SPF male Sprague-Dawley rats, aged 2-3 months, weighing 200-250 g, were randomly di- vided into 3 groups： control group （group C, n = 10）, scald group （group S, n = 10） and MDP group （ n = 30）. The rats were subjected to a third-degree scald burn covering 20% of total body surface area in groups S and MDP. The rats were only exposed to 20 ℃ water in group C. MDP 5 mg/kg was injected via the femoral vein at 24 h after scald burn in group MDP. Arterial blood samples were collected at 1, 6 and 24 h after MDP injection in group MDP, at 24 h after scald burn in group S, or at 24 h after exposure to 20 ℃ water in group C for blood gas analys- is and for measurement of white blood cell （WBC） and ptatelet （Ph） counts, serum aminotransferase （ALT）, as- partate transferase （AST）, total bilirnbin （TB）, creatinine （Cr） and blood urea nitrogen （BUN） levels, creatine kinase isoenzyme-MB （CK-MB） activity, and plasma tumor necrosis factor-α （TNF-α）, interferon-γ （IFN-γ）, in-terleukin-6 （IL-6）, IL-10 and high mobility group box 1 protein （HMGB-1） levels. The rats were sacrificed after collecting blood samples, and heart, liver, lung, and kidney specimens were obtained for microscopic examination of pathologic changes. The activity of myeloperoxidase （MPO） in lung tissues was measured. Another 90 male Sprague-Dawley rats were randomly divided into 3 groups and treated as the method previously described for record of the survival rate within 72 h. Results Compared with C grotlp, the plasma IL-6, IL-10, IFN-γ and HMGB1 levels, WBC count, serum ALT, AST, and BUN levels and MPO activity were significantly increased, and the survival rate within 72 h was decreased in S group, and the plasma TNF-α, IL-6, IL-10, IFN-γ and HMGB-1 lev- els, serum ALT, AST, TB, BUN, Cr and CK-MB levels, MPO activity, PaCO2 and BE value were significantly increased, and WBC and PLT counts, pH value, PaO2 and survival rate within 72 h were decreased in MDP group （P 〈0.05）. Compared with S group, tire plasma TNF-α, IL-6, IFN-γ and HMGB-1 levels, serum ALT, AST, TB, BUN, Cr and CK-MB levels, MPO activity, PaCO2 and BE value were significantly increased, and WBC and Ph counts, pH value, PaO2 and survival rate within 72 h were decreased in MDP group （ P 〈 0：05）. Tire patho- logic changes of heart, liver, lung and kidney were obvious in S and MDP groups and severer in MDP group. Con- clusion After a third-degree 20% total body surface area scald burn, MDP induces excessive production of in- flammatory cytokines accompanying with muhiple organ damage ; thus the model of sepsis is successfully established after scald burn in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2013年第4期481-484,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金青年科学基金（81101449）
中央高校基本科研业务费专项资金（111058）
湖北省自然科学基金（2010CDB00404）
