腹腔注射人粪便悬液建立大鼠脓毒症及严重脓毒症模型

Rat models of sepsis and severe sepsis were established by intraperitoneal injection of human stool suspension

目的:建立标准化的、可复制的脓毒症及严重脓毒症大鼠模型。方法:健康雄性SPF级SD大鼠72只,随机分为3组:假手术组(C组)、脓毒症组(S组)、严重脓毒症组(SS组)。S组和SS组分别取1.6 mL/kg和4 mL/kg人粪便悬液,生理盐水稀释至3 mL腹腔注射。C组注射生理盐水。术后观察动物一般情况,记录48 h生存时间,于7 h进行疾病严重程度评估,颈动脉插管监测平均动脉压(MAP),取血检测血气分析、乳酸、ALT、AST,Creat、BUN、CK、CK-MB、IL-6、IL-10水平,行血培养,观察其心、肝、肺、肾病理变化。结果:疾病严重程度评估S组处于轻中度,SS组处于中重度。SS组生存时间明显低于S组(P<0.01)。与C组比较,S组和SS组MAP、PaCO2、HCO3-、BE降低,BUN升高(均P<0.05),SS组pH、PO2、SaO2降低,LAC、ALT、AST、Creat、CK升高(均P<0.05);S组IL-6及IL-10浓度升高(均P<0.05),SS组IL-6和IL-10浓度显著升高(均P<0.01)。S组和SS组血培养均为大肠埃希菌。SS组组织病理损伤明显较S组严重。结论:该模型符合脓毒症及严重脓毒症模型的基本特点,且标准化、可复制,可用于研究。

Objective ： To establish a standardized and replicable rat models of sepsis and severe sepsis. Methods ： Seventy-two healthy male SD rats were divided into three groups randomly： sham operation group （C group） , sepsis group （ S group） and severe sepsis group （ SS group）. For induction of sepsis and severe sepsis, 1.6 ml/kg or 4 ml/kg of human stool suspension, diluted in saline to 3 ml, were injected into abdominal cavity respectively. Intraperitoneal injection of equal normal amount of saline were given to the C group. After models were established, general condition and 48 hours survival rate of the rats were observed. The severity of the disease were evaluated 7 hours after the models were established, including invasive mean arterial pressure （MAP） , arterial blood gas indexes （ pH, PaCO2, SaO2, BE, HCO3 -）, arterial lactic acid （LAC）, liver function（ALT, AST）, kidney function （Creatinine or Cr, BUN）, myocardial injury markers （ CK, CK-MB） , serum cytokines （ IL-6, IL-10 ） ; blood was cultured also. Finally, rats were executed with sodium pentobarbital. Heart, liver, lung and kidney were observed by microscopic pathological examinations. Results： Compared with S group, more serious general condition in SS group was observed. The survival time of S group was significantly longer than that of SS group （ P 〈 0.01 ）. S group was in low or mid-grade, SS group was in mid or high-grade in respect of disease severity. The MAP, PCO2, HCO3 - , BE of S group and SS group were lower than those of C group （ P 〈 O. 05 ）, the BUN of S group and SS group were higher than that of C group （ P 〈 0.05）. Compared with C group, pH, PO2, SaO2 of SS group showed a reduction, LAC, ALT, AST, Creatinine or Cr, CK of SS group showed an increase （P 〈 0.05）. The serum concentrations of IL-6 and IL-10 in S and SS group were higher than those of C group, especially in SS group, which were higher than those in S group （ P 〈 0.01 ）. Eseherichia coli were identified in both of S and SS group. There were pathological changes in tissues of S and SS group, and the changes were significantly more severe in SS group than that in S group. Conclusion： The models accord with the basic characteristics of sepsis and severe sepsis, and are standardized and replicable, so can be used in experimental study.