背景:脓毒症是一种复杂的疾病,其特征是由感染引起的全身性宿主炎症。实验和观察性研究表明,肥胖,代谢综合征(MetS)的组成部分之一,或阿司匹林(ASA)治疗可能与脓毒症生存有关。然而,尚未研究ASA对MetS诱导的脓毒症小鼠的影响。
方法:瑞士小鼠在其生命的前5天给予味精(MSG)(4mg/kg)进行MetS诱导,而对照小鼠接受等摩尔的盐水溶液。MetS在其第60天的雄性小鼠中进行了验证。在败血症之前给予ASA治疗15天(40mg/kg)。在第75天,通过盲肠结扎穿孔(CLP)在MetS和对照小鼠中诱导脓毒症。通过确定存活率来评估ASA对MSG诱导的MetS脓毒症小鼠的影响。一氧化氮(NO)的定量,和血浆中的细胞因子水平,虽然这些数据与血液学相关,血糖和心血管参数。
结果:通过Lee-Index(3体重/鼻肛门长度×1000)验证了MetS,高血压,和新生儿接受味精的动物的高血糖。在对照动物中,严重脓毒症促进低血糖,这与死亡率有关,以及增加的血浆NO水平,低血压,血液学改变,和促炎细胞因子的升高。相比之下,MetS和ASA预处理能够预防脓毒症相关的改变。
结论:MetS和ASA预处理对严重脓毒症具有保护作用。然而,ASA在患有严重脓毒症的MetS的小鼠中无效。
BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored.
METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters.
RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations.
CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.