参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用研究

目的探讨参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用。方法国产健康雄性白猪21头,采用随机数字表法分为假手术组(Sham组,n=5)、创伤性心脏骤停复苏(TCA组,n=9)和参附组(SFI组,n=7)。Sham组只经历气管插管及动静脉置管,不经历放血、复苏等过程。TCA组匀速释放总血容量的40%,然后经电刺激法室颤5 min,心肺复苏5 min后常规液体复苏治疗。SFI组在TCA组基础上于复苏后5 min进行参附注射液的干预。于放血前10 min、复苏后1、3、6、24 h检测血清TNF-α、IL-6、肌酐(Cr)、尿素氮(BUN)水平。复苏后24 h经右侧耳缘静脉注射10%氯化钾液20 mL处死猪,迅速获取肾组织标本,应用原位末端标记法(TNUEL法)检测细胞凋亡情况,免疫组织化学法检测半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的蛋白表达水平。结果TCA组中有8头猪复苏成功,SFI组和Sham组中所有猪复苏成功。与Sham组比较,TCA组血清Cr水平在复苏后24 h、BUN水平在复苏后1、3、6、24 h均明显增高(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显增高(均P<0.05),复苏后24 h后肾组织细胞凋亡指数及Caspase-3表达增加(均P<0.05)。与TCA组比较,SFI组BUN水平复苏后3、6 h明显降低(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显降低(均P<0.05),肾组织细胞凋亡指数和Caspase-3蛋白表达有所降低,但差异无统计学意义(均P>0.05)。结论在猪TCA复苏模型中,早期应用参附注射液能够明显减轻复苏后肾损伤。其机制可能与抑制系统炎症反应、减轻细胞凋亡有关。

Protective Effects of Shenfu Injection on Kidney Injury after Traumatic Cardiac Arrest in Porcine Model

Objective To investigate protective effects of Shenfu Injection on kidney injury after traumatic cardiac arrest in a porcine model.Methods Totally 21 male domestic pigs were divided into three groups according to random digit table:Sham operation group(Sham group,n=5),traumatic cardiac arrest group(TCA group,n=9),and Shenfu Injection group(SFI group,n=7).The pigs in the Sham group only experienced tracheal intubation and surgical operation without the process of blood loss and resuscitation.In the TCA groups,40%estimated blood volume removed at a constant speed,then the pigs were subjected to 5 min of untreated ventricular fibrillation and 5 min of cardiopulmonary resuscitation(CPR).Coincident with the start of CPR,conventional fluid resuscitation was initiated.SFI was intravenously administered at 5 min after resuscitation additionally in the SFI group.The concentration of creatinine(Cr),blood urea nitrogen(BUN),tumor necrosis TNF-αand IL-6 in serum were measured at baseline and at 1,3,6 and 24 h after resuscitation.After the pigs sacrificed by 20 mL 10% potassium chloride intravenously via right marginal auricular vein at 24 h after resuscitation,the tissue of kidneywas rapidly obtained for the determination of cell apoptosis by TUNEL and Caspase-3 expression by immunohistochemistry.Results Eight pigs in the TCA group and all pigs in both SFI and Sham group were successfully resuscitated. Compared withSham group,the Cr level at 1 h and BUN level at 1,3,6 and 24 h in the TCA group were significantly increased ( allP <0. 05) ,the TNF-α and IL-6 levels in TCA group were significantly increased at 3,6 and 24 h after resuscitation ( allP <0. 05);the kidney apoptosis index and expression of Caspase-3 were both increased in TCA group at 24 h after resuscitation( allP <0. 05) . Compared with TCA group,the BUN level at 3,6 h in the SFI group were significantly decreased ( allP <0. 05);both the TNF-α and IL-6 levels in the SFI group were significantly decreased at 3,6 and 24 h ( allP <0. 05);boththe kidney apoptosis index and expression of Caspase-3 in the SFI group were decreased,but the difference was not statisticallysignificant ( allP >0. 05) . Conclusion In a porcine model of traumatic cardiac arrest and resuscitation,early applicationof SFI can significantly alleviate post-resuscitation kidney injury,which may be related to inhibition of systemic inflammatoryresponse and cell apoptosis.