青蒿琥酯减轻猪心肺复苏后肾、肠器官损伤的作用研究

Effect of Artesunate on Reducing Renal and Intestinal Injury after Cardiopulmonary Resuscitation in Porcine

目的探讨青蒿琥酯(ART)对猪心肺复苏(CPR)后肾、肠器官损伤的作用,并探讨其作用机制。方法选择健康雄性白猪24头,随机分为3组,分别为假手术组(Sham组,n=6),CPR组(n=10),ART组(n=8);Sham组只进行实验准备;另两组经右心室放电诱导心室颤动9 min,再进行CPR 6 min的方法建立动物模型。ART组在复苏后5 min时经右股静脉输注青蒿琥酯(4.8 mg/kg),其他两组均给予相同剂量的溶媒。检测造模前后血肌酐(Cr)、尿素氮(BUN)、肠型脂肪酸结合蛋白(IFABP)及二胺氧化酶(DAO)水平;复苏后ELISA检测肾、肠组织肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)表达,TUNEL法观察细胞凋亡并计算肾、肠组织细胞凋亡程度。结果Sham组肾、肠组织细胞正常,CPR组可见较多棕黄色细胞,组织细胞大量凋亡,ART组中可见少量棕黄色细胞,较CPR组明显减少,细胞凋亡减少。与本组造模前比较,CPR、ART组造模后1、2、4、24 h血清Cr、BUN、IFABP、DAO水平升高(P<0.05)。与Sham组同期比较,CPR组复苏后1、2、4、24 h血清Cr、BUN、IFABP、DAO水平及肾、肠组织细胞凋亡指数、TNF-α、IL-1β表达升高(P<0.05)。与CPR组同期比较,ART组复苏后1、2、4、24 h血清Cr、BUN、IFABP、DAO水平及肾、肠组织细胞凋亡指数、TNF-α、IL-1β表达下降(P<0.05)。结论应用青蒿琥酯可显著降低猪心脏骤停模型复苏后肾脏和肠道损伤,其机制可能与减轻组织炎症反应及细胞凋亡等有关。

Objective To investigate the effect of artesunate(ART)on renal and intestinal injury after cardiopulmonary resuscitation(CPR)in porcine,and to explore its mechanism.Methods A total of 24 healthy male white porcines were randomly divided into 3 groups:Sham group(n=6),CPR group(n=10)and ART group(n=8).Sham group was only prepared for the experiment.The other 2 groups established animal models by inducing ventricular fibrillation through right ventricular discharge for 9 minutes and CPR for 6 minutes.Artesunate(4.8 mg/kg)was infused into the right femoral vein 5 minutes after resuscitation in ART group,and the other 2 groups were given the same amount of solvent.Serum creatinine(Cr),urea nitrogen(BUN),intestinal fatty acid binding protein(IFABP)and diamine oxidase(DAO)were measured before and after modeling.The expressions of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in renal and intestinal tissues were detected by ELISA after CPR,cell apoptosis was observed by TUNEL,and the degree of apoptosis in renal and intestinal tissues were calculated.Results In Sham group,the renal and intestinal tissue cells were normal,while in CPR group,there were more brown chloragogen cell and a lot of apoptosis,and in ART group,there were a few brown chloragogen cell,which was significantly less than that in CPR group,and the apoptosis was reduced.Compared with the group before modeling,the levels of serum Cr,BUN,IFABP and DAO in CPR and ART group increased at the 1st,2nd,4th and 24th hour after modeling(P<0.05).Compared with Sham group,the levels of serum Cr,BUN,IFABP and DAO,and the expressions of apoptosis index,TNF-αand IL-1βin renal and intestinal tissues increased in CPR group at the 1st,2nd,4th and 24th hour after resuscitation(P<0.05).Compared with CPR group,the levels of serum Cr,BUN,IFABP and DAO,apoptosis index,and the expressions of TNF-αand IL-1βin renal and intestinal tissues decreased in ART group at the 1st,2nd,4th and 24th hour after resuscitation(P<0.05).Conclusion ART can significantly reduce the renal and intestinal injury after resuscitation in the resuscitation model of porcine cardiac arrest,which may be related to the reduction of tissue inflammatory response and apoptosis.