全身炎症反应综合征动物模型发病机制的研究

Pathogenesis of Animal Models of Systemic Inflammatory Response Syndrome

目的通过建立全身炎症反应综合征(SIRS)大鼠模型,探讨多器官功能障碍综合征(MODS)可能的发病机制。方法采用腹腔注射酵母多糖悬液方法复制大鼠SIRS模型,雄性SD大鼠共50只,随机分成正常对照组(正常对照组,20只)和腹腔注射酵母悬液组(注射酵母悬液组,30只)。观察各组大鼠的症状、体征、血气、肺、肝、小肠病理及电镜改变、血清及肺泡灌洗液的细胞因子的变化。结果注射酵母悬液组大鼠的症状、体征均有明显变化,与正常对照组比较差异有统计学意义(P<0.05);注射酵母悬液组大鼠动脉血氧分压及氧合指数明显降低,与正常对照组比较差异有统计学意义(P<0.05);注射酵母悬液组大鼠肺、肝及小肠脏器病理及电镜改变明显,均出现以急性炎症为主的非特异性病理损害;注射酵母悬液组大鼠血清及肺泡灌洗液的肿瘤坏死因子(TNF-α)、干扰素(IFN)、IL-4、IL-10、IL-18水平均显著升高,与正常对照组比较差异均有统计学意义(P<0.05)。结论以腹腔注射酵母多糖悬液的方法可成功复制出SIRS模型,对发病机制的探讨为进一步MODS的临床研究提供了实验基础。

Objective To investigate the possible pathogenesis of multiple organ dysfunction syndrome（MODS） through establishing the rat models of systemic inflammatory response syndrome（SIRS）.Methods SIRS rat model was set up by intraperitoneal injection of zymosan suspension.Totally 50 male SD rats were randomly divided as control group received no shock（n=20）,and trial group received intra-peritoneal injection of zymosan（n=30）.The indexes of the examination included behaviors and symptoms,arterial partial pressure of oxygen（PaO2）,oxygenation index（PaO2/FiO2）,pathological alteration of the lung,liver and small intestine,levers of cytokine in alveolar macrophage and serum.Results Compared with the control group,in the trial group significant variation of behaviors and symptoms were observed（P〈0.05）;the levels of PaO2 and PaO2/FiO2 were significantly lower;（P〈0.05）.non-specific pathological injuries mainly as acute inflammation were observed under both microscope transmission electron microscope in the lung,liver and small intestine in the trial group;the levels of TNF-α,IFN,IL-4,IL-10,IL-18 expressions in alveolar macrophage and serum were dramatic increased（P〈0.05）.Conclusion Zymosan injection can be used to set up a simple animal model for SIRS to study the pathogenesis of SIRS,which provides some experimental basis for the clinical study of MODS.