脓毒症相关脏器损伤动物模型研究进展  

Research Progress on Animal Models of Sepsis-Related Organ Injury

作　　者：杨家豪 丁纯蕾[1] 钱风华[2] 孙旗 姜旭升 陈雯 沈梦雯[1] YANG Jiahao;DING Chunlei;QIAN Fenghua;SUN Qi;JIANG Xusheng;CHEN Wen;SHEN Mengwen(Department of Emergency Medicine,Yueyang Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Department of Geriatrics Medicine,Yueyang Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院急诊医学科,上海200437 [2]上海中医药大学附属岳阳中西医结合医院老年医学科,上海200437

出　　处：《实验动物与比较医学》2024年第6期636-644,共9页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金“基于机械敏感离子通道蛋白PIEZO1的四逆升降散调控细胞紧密连接改善脓毒症急性肺损伤的机制研究”(82304933);上海市卫生健康委员会卫生行业临床研究专项“四逆升降散改善脓毒症急性呼吸窘迫综合征患者预后的临床观察研究”(202140202);上海中医药大学预算内科研项目“加味四逆升降散调控Ang-Tie轴改善脓毒症急性肺损伤毛细血管渗漏的研究”(2021LK096)。

摘　　要：脓毒症是机体因感染和免疫失调引起的多脏器功能衰竭综合征,影响心脏、肺脏、肾脏、肝脏、大脑等多个重要器官,致死率极高。建立各器官功能衰竭综合征相应的动物模型是明确其发病机制、研究潜在有效药物及评估治疗方案有效性与安全性不可或缺的一环。本文首先对脓毒症相关脏器损伤的经典造模方式进行总结,指出脓毒症的经典造模方式包括破坏肠道屏障组织完整性和植入病原体或毒性药物。前者主要包括盲肠结扎穿刺法、升结肠植入支架法和盲肠结扎切口法,后者根据模拟临床感染途径的不同分为腹腔注射、静脉注射和气道内给药,其中以盲肠结扎穿刺法和脂多糖腹腔注射最为常见。其次,本文归纳总结了脓毒症致心肌损伤、急性肺损伤、急性肾损伤、急性肝损伤、脓毒症相关脑病的动物模型常见的造模方法和模型评估方法,指出几乎所有器官损伤都用到了经典造模方式,对不同器官损伤模型根据发病机制的不同进行了相应的补充。比如,除经典造模方式外,气管内滴注脂多糖进行脓毒症致急性肺损伤的造模方式更能模拟肺屏障功能损伤;盲肠结扎穿刺法后气管内给予假单胞菌进行二次打击的脓毒症致急性肾损伤造模方式能表现出更严重的急性肾损伤;半乳糖胺腹腔注射是较为成熟的脓毒症致急性肝损伤的造模方式;颅内注射脂多糖是脓毒症致脑功能障碍可行的造模方式。另外,除造模方式不同外,根据实验目的的不同,给药时间、给药剂量和实验时间节点也均存在差异。本综述通过对脓毒症致心肌病、急性肺损伤、急性肾损伤、急性肝损伤、脑功能障碍的动物模型研究进展进行介绍,以期为动物模型的选择和实验设计的优化提供一定参考。Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction,with a high mortality rate.It affects multiple important organs such as the heart,lungs,kidneys,liver,and brain.Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis,researching potential effective drugs,and evaluating the effectiveness and safety of treatment plans.This article first summarizes classic modeling methods for sepsis related organ injury,including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs.The former mainly includes cecal ligation and puncture,ascending colon stent implantation,and cecal ligation incision.The latter is divided into intraperitoneal injection,intravenous injection,and intratracheal administration based on the clinical infection route being simulated.Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods.Secondly,this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy,acute lung injury,acute kidney injury,acute liver injury,and brain dysfunction.It points out that almost all organ injuries use classic modeling methods,and different organ injury models have additional modifications according to their different pathogenesis.For example,in addition to the classic modeling methods,lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction.Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury.Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury.Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy.In addition to the different modeling methods,there are differen

关 键 词：脓毒症 动物模型 多器官功能损伤 研究进展 

分 类 号：R-332[医药卫生] Q95-33[生物学—动物学]