复合感染脓毒症模型大鼠的炎症与凝血功能紊乱进程  

Development of inflammation and coagulation disorders in sepsis

作　　者：侯媛璐 赵茹茹 高磊 李奇峰 姚政 李明泓 HOU Yuanlu;ZHAO Ruru;GAO Lei;LI Qifeng;YAO Zheng;LI Minghong(Basic Medicine College,Yunnan University of Chinese Medicine,Kunming 650500,China;Research and Innovation Team in University of Yunnan Province on the Relationship between Treatment Methods and Efficacy of Traditional Chinese Medicine,Kunming 650500,China;Yunnan Key Laboratory of Chronic Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学基础医学院,昆明650500 [2]云南省高校中医治法与中药药效关系研究科技创新团队,昆明650500 [3]云南省中西医结合慢病防治重点实验室,昆明650500

出　　处：《中国实验动物学报》2024年第2期230-237,共8页Acta Laboratorium Animalis Scientia Sinica

基　　金：云南省科学技术厅-云南中医药大学应用基础研究联合专项(202001A2070001-032);云南省教育厅科学研究基金(2023Y0441)。

摘　　要：目的探讨脓毒症病程中凝血功能和炎症水平的改变。方法通过改良盲肠结扎穿刺术(cecal ligation and puncture,CLP)构建复合感染脓毒症大鼠模型(multiple infection sepsis model,MIM),将48只雄性SD大鼠随机分为空白组(Control组,n=8)、假手术组(Sham组,n=8)、复合感染脓毒症模型4 h(4 h组,n=8)、8 h(8 h组,n=8)、12 h(12 h组,n=8)、16 h(16 h组,n=8)组,检测炎症指标和凝血相关指标。结果(1)所有脓毒症模型大鼠脂多糖(lipopolysaccharide,LPS)及白介素-6(interleukin-6,IL-6)含量较Sham组均显著升高(P<0.001),且术后随时间延长,LPS及IL-6含量逐渐升高,12 h后LPS无明显变化;(2)脓毒症模型病程中后期组(8 h及以后)凝血酶原时间(prothrombin time,PT)较Sham组明显延长(P<0.01);(3)与Sham组相比,8 h组、12 h组、16 h组活化部分凝血酶原时间(activated partial thromboplastin time,APTT)时间显著延长(P<0.05,P<0.01),且8 h后APTT逐渐延长接近Control组;(4)8 h后(不含8 h)纤维蛋白原(fibrinogen,Fbg)含量较Sham组显著增加(P<0.01);(5)脓毒症病程各时间段组均与Control组纤维蛋白降解产物(fibrin degradation products,FDP)具有显著性差异(P<0.01),而与Sham组无显著性差异;(6)脓毒症病程各时间段组抗凝血酶-Ⅲ(antithrombin-Ⅲ,AT-Ⅲ)较Sham组均显著降低(P<0.01),且AT-Ⅲ随病程呈下降趋势,其中4 h组及8 h组与16 h组比存在显著性差异。结论MIM大鼠模型可较好地反映脓毒症病程中炎症与凝血紊乱的发展趋势与相互关系,可更好的为探究脓毒症病程发展提供研究基础。Objective To investigate changes in coagulation function and inflammation levels during sepsis.Methods A rat model of sepsis was established using the multiple infection sepsis model(MIM)based on cecal ligation and puncture.Forty-eight male Sprague-Dawley rats were assigned randomly to the following groups:control group,sham group,4 h sepsis group,8 h sepsis group,12 h sepsis group,and 16 h sepsis group(n=8 per group).Inflammatory markers and coagulation-related indicators were measured by enzyme-linked immunosorbent assay and coagulation analysis.Results(1)Lipopolysaccharide(LPS)and interleukin-6(IL-6)levels were significantly higher in the model rats at all time points compared with the sham group(P<0.001).LPS and IL-6 levels increased gradually with disease progression,with no further changes in LPS after 12 hours.(2)Prothrombin time(PT)was significantly prolonged in the middle and late stages of the sepsis model,starting from 8,compared with the sham group(P<0.01).(3)Partially activated prothrombin time(APTT)time was significantly prolonged in the 8,12,and 16 h groups compared with the sham group(P<0.05,P<0.01).APTT gradually lengthened from 8 h,but approached control levels thereafter.(4)Fibrinogen(Fbg)content was significantly higher in all sepsis groups,except for the 8 h group,compared with the sham group(P<0.01).(5)Fibrin degradation products(FDP)differed significantly between the control and sham groups(P<0.01),but not between the sham and sepsis groups.(6)Antithrombin-Ⅲ(AT-Ⅲ)levels decreased significantly throughout each stage of sepsis progression compared with the sham group(P<0.01),and AT-Ⅲshowed a downward trend with the course of disease,with significant differences among the 4,8,and 16 h groups.Conclusions The MIM rat model can reflect the development of inflammatory and blood coagulation disorders and their relationship during the course of sepsis,and may thus provide a good foundation for further research into the disease course of sepsis.

关 键 词：脓毒症 疾病进程 炎症 凝血 多器官功能衰竭 

分 类 号：Q95-33[生物学—动物学]