4-苯基丁酸对大鼠脓毒症的保护作用

Protective effect of 4-phenylbutyric acid in sepsis rats

目的探讨内质网应激抑制剂4-苯基丁酸(PBA)对大鼠脓毒症的保护作用。方法 160只SD大鼠,雌雄各半,分为假手术组、脓毒症组、常规治疗组、PBA(5mg/kg)早期治疗组和PBA(5mg/kg)晚期治疗组。采用盲肠结扎穿孔术(CLP)复制脓毒症模型;常规治疗组在CLP 12h后输注乳酸林格氏液;PBA早期治疗组在CLP手术完成后立即尾静脉给予PBA;PBA晚期治疗组在CLP 12h后股静脉输注PBA。观察各组对脓毒症大鼠组织灌注、器官功能以及存活时间、存活率的影响。结果脓毒症后,大鼠的肾脏和肠道功能明显受损;常规治疗可部分恢复肾脏和肠道功能;PBA早期和晚期治疗均可显著改善肾脏和肠道功能,体现在肾脏和肠道功能的指标,包括尿素氮、血肌酐、β2微球蛋白和视黄醇结合蛋白、D乳酸和内毒素均显著降低;同时PBA治疗明显增加肾脏和肠道的血流量,增加器官灌注,延长动物的存活时间,提高存活率。其中PBA早期治疗组的平均存活时间为16.32h,72h存活率为25%;PBA晚期治疗组的平均存活时间为13.11h,72h存活率为31%。结论 PBA对大鼠脓毒症有较好的保护作用。

Objective To investigate the protective effect of the endoplasmic reticulum stress inhibitor（ 4-phenylbutyric acid,PBA） in sepsis rats. Methods Totally 160 SD rats（ 80 females and 80 males） were divided into sham operation group,sepsis group,conventional treatment group,early PBA treatment group and late PBA treatment group. The sepsis model was replicated by cecal ligation and puncture（ CLP）; the conventional treatment group was transfused to LR at 12 hours after CLP,the early PBA treatment group was given PBA in the tail vein immediately after the completion of the CLP operation,and the late PBA treatment group was injected PBA in the femoral vein at 12 hours after CLP. The effects of each group on tissue perfusion,organ function,survival time and survival rate were observed. Results After sepsis,the intestines and kidney function were significantly impaired; conventional treatment（ including fluids,anti-infection and vasoactive drugs） could in partly improve the intestines and kidney function; early or later administration of PBA could improve the intestines and kidney function significantly,and the indicators of intestines and kidney function decreased,including urea nitrogen,serum creatinine,β2-microglobulin,retinol binding protein,D-lactate and endotoxin. While early or later administration of PBA could increase the blood flow of intestines and kidney,prolong the survival time,and increase animal survival rate. Compared with conventional treatment,the survival time of early administration of PBA group was 16. 32 hours,and the 72 h survival rate was 25%; the survival time of the late administration of PBA group was 13. 11 hours,and the 72 h survival rate was 31%. Conclusion PBA has protective effects in sepsis rats.