Cecal Ligation Puncture Procedure
Cecal Ligation Puncture Procedure
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DOI：
10.3791/2860
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发表时间：
2011-05-01
影响因子：
1.2
通讯作者：
Gamero, Ana M.
中科院分区：
文献类型：
--
作者：
Toscano, Miguel G.;Ganea, Doina;Gamero, Ana M.
人类脓毒症的特征是一系列系统性反应，以响应不能被宿主局部控制的密集和大规模感染。目前，脓毒症是美国重症监护病房的十大死亡原因之一（1）。在脓毒症期间，存在两个可能重叠的既定血液动力学阶段。初始阶段（高动力）定义为巨噬细胞和中性粒细胞大量产生促炎细胞因子和活性氧，影响血管通透性（导致低血压）、心脏功能并诱导最终导致组织坏死和器官衰竭的代谢变化。因此，最常见的死亡原因是急性肾损伤。第二阶段（动力减退）是抗炎过程，涉及单核细胞抗原呈递改变、淋巴细胞增殖和功能降低以及细胞凋亡增加。这种被称为免疫抑制或免疫抑制的状态急剧增加了Nocosomial感染的风险，并最终导致死亡。这些病理生理过程的机制还没有得到很好的表征。由于脓毒症的两个阶段都可能导致不可逆和不可修复的损害，因此必须确定患者的免疫和生理状态。这是许多治疗药物失败的主要原因。在脓毒症的不同阶段给予相同的药物可能是治疗性的或有害的或没有效果（2，3）。要了解不同水平的脓毒症，关键是要有一个合适的和全面的动物模型，再现疾病的临床过程。研究脓毒症发生的病理生理机制和控制模型条件对于检测潜在的治疗药物是非常重要的。为了研究人类脓毒症的病因学，研究人员开发了不同的动物模型。最广泛使用的临床模型是盲肠结扎穿孔（CLP）。CLP模型由盲肠穿孔组成，允许粪便物质释放到腹膜腔中，以产生由多种微生物感染诱导的加剧的免疫应答。该模型符合临床相关的人体条件。如在人类中一样，经历CLP伴液体复苏的小鼠显示出第一（早期）高动力期，其及时进展到第二（晚期）低动力期。此外，细胞因子谱与人脓毒症中观察到的相似，其中淋巴细胞凋亡增加（综述见4，5）。由于脓毒症涉及多种和重叠的机制，研究人员需要一个合适的脓毒症模型的控制严重程度，以获得一致的和可重复的结果。
Human sepsis is characterized by a set of systemic reactions in response to intensive and massive infection that failed to be locally contained by the host. Currently, sepsis ranks among the top ten causes of mortality in the USA intensive care units (1). During sepsis there are two established haemodynamic phases that may overlap. The initial phase (hyperdynamic) is defined as a massive production of pro inflammatory cytokines and reactive oxygen species by macrophages and neutrophils that affects vascular permeability (leading to hypotension), cardiac function and induces metabolic changes culminating in tissue necrosis and organ failure. Consequently, the most common cause of mortality is acute kidney injury. The second phase (hypodynamic) is an anti-inflammatory process involving altered monocyte antigen presentation, decreased lymphocyte proliferation and function and increased apoptosis. This state known as immunosuppression or immune depression sharply increases the risk of nocosomial infections and ultimately, death. The mechanisms of these pathophysiological processes are not well characterized. Because both phases of sepsis may cause irreversible and irreparable damage, it is essential to determine the immunological and physiological status of the patient. This is the main reason why many therapeutic drugs have failed. The same drug given at different stages of sepsis may be therapeutic or otherwise harmful or have no effect (2,3). To understand sepsis at various levels it is crucial to have a suitable and comprehensive animal model that reproduces the clinical course of the disease. It is important to characterize the pathophysiological mechanisms occurring during sepsis and control the model conditions for testing potential therapeutic agents.To study the etiology of human sepsis researchers have developed different animal models. The most widely used clinical model is cecal ligation and puncture (CLP). The CLP model consists of the perforation of the cecum allowing the release of fecal material into the peritoneal cavity to generate an exacerbated immune response induced by polymicrobial infection. This model fulfills the human condition that is clinically relevant. As in humans, mice that undergo CLP with fluid resuscitation show the first (early) hyperdynamic phase that in time progresses to the second (late) hypodynamic phase. In addition, the cytokine profile is similar to that seen in human sepsis where there is increased lymphocyte apoptosis (reviewed in 4,5). Due to the multiple and overlapping mechanisms involved in sepsis, researchers need a suitable sepsis model of controlled severity in order to obtain consistent and reproducible results.