摘要
目的建立一种更符合临床脓毒症生理机制的盲肠结扎穿孔动物模型。方法SPF级雄性SD大鼠96只,采用随机数字分组法分为假手术组(n=24)、置管组(n=24)、盲肠结扎穿刺(CLP)组(n=24)、CLP+置管组(n=24),观察造模后24 h各组病死率,造模后24 h开腹观察腹腔状况,观察大鼠心、肺、肝、肾组织的病理学形态改变及各组织损伤病理积分。取下腔静脉血检测全血白细胞(WBC)、血小板(PLT)值;检测血清白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α水平,检测血清肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和肌酐(CREA)、尿素氮(BUN)水平。取主动脉血进行血气分析。结果假手术组和置管组大鼠24 h无病死率,CLP组大鼠24 h病死率20.8%,CLP+置管组大鼠24 h病死率54.2%。CLP+置管组心、肺、肝、肾组织均呈现以肿胀、炎性细胞浸润为主的病理学改变,CLP组多数出现单个脏器炎性细胞浸润,假手术组和置管组各脏器未出现明显肿胀及炎性细胞浸润;大鼠心肌组织病理学评分、肺组织损伤病理学评分、肾组织损伤病理学评分假手术组和置管组均低于CLP组及CLP+置管组(P均=0.000);大鼠肝组织损伤病理学评分假手术组均低于置管组、CLP组及CLP+置管组(P均=0.000);TNF-α水平、PaO2水平、CK-MB含量、cTnT含量、AST含量、TBIL含量、BUN含量、CREA含量等的两两比较结果显示,假手术组分别与置管组、CLP组、CLP+置管组比较,置管组分别与CLP组、CLP+置管组比较,差异均有统计学意义(P均=0.000);pH水平的两两比较结果显示,假手术组分别与置管组、CLP组比较,置管组分别与CLP组、CLP+置管组比较,差异均有统计学意义(P均=0.000)。结论虽然CLP组和CLP+置管组模型都能较好地模拟脓毒症的病理生理机制,但CLP+置管组出现明显的多器官功能障碍,运用CLP+置管组可复制出更接近临床实际的腹腔感染诱发的脓毒症致多器官功能障碍的动物模型。
Objective To establish an improved animal model of sepsis induced by cecal ligation and puncture(CLP).Methods Ninety-six male Sprague-Dawley rats were randomly divided into sham operation group(n=24),intubation group(n=24),CLP group(n=24),and CLP+intubation group(n=24).The mortality rate,abdominal cavity condition,pathological changes and pathological scores of heart,lungs,liver,and kidneys of rats in each group were observed after modeling.Blood samples were obtained from the inferior vena cava for measuring the whole blood cells(WBC)and platelets(PLT)counts and analyzing serum interleukin(IL)-6,tumor necrosis factor(TNF)-α,serum troponin T(cTnT),creatine kinase-MB(CK-MB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CREA),and blood urea nitrogen(BUN)levels.Blood gas analysis of the aorta was also performed.Results The mortality rates 24 h after modeling were 0 in sham operation group and intubation group,20.8%in CLP group,and 54.2%in CLP+intubation group.Pathologically,swelling and inflammatory cell infiltration in the heart,lungs,liver,and kidneys were seen in the CLP+intubation group,inflammatory cell infiltration in a single organ was seen in most rats in the CLP group,and no obvious swelling and infiltration of inflammatory cells was observed in the sham-operation group and intubation group.The myocardial histopathology score,lung tissue injury pathology score,and kidney tissue injury pathology score in both the sham-operation group and the intubation group were significantly lower than those in the CLP group and the CLP+intubation group(all P=0.000).TNF-α,PaO2,CK-MB,cTnT,AST,TBIL,BUN,and CREA were significantly different between sham-operation group and intubation group/CLP group/CLP+intubation group and between intubation group and CLP group/CLP+intubation group(all P=0.000).The pH level was significantly different between sham operation group and intubation group/CLP group,between intubation group and CLP group/CLP+intubate group(all P=0.000).Conclusions Although both CLP and CLP+intubation can well mimic the pathophysiological mechanism of sepsis in rats,multiple organ dysfunction occurs in the latter.Thus,CLP+intubation can establish animal models of multiple organ dysfunction caused by sepsis induced by clinically effective abdominal infection.
作者
黎李俊
杨国辉
LI Lijun;YANG Guohui(Clinical Medicine College of Guizhou Medical Unicersity,Guiyang 550001,China;Intensive Care Unit,Affiliated Hospital of Guizhou Medical University,Guiyang 550001,China)
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2020年第4期468-476,共9页
Acta Academiae Medicinae Sinicae