Islam Anowarul, Kim So Eun, Yoon Jae Chol, Jawad Ali, Tian Weishun, Yoo Yeo-Jin, Kim In-Shik, Ahn Dongchoon, Park Byung-Yong, Hwang Yong, Lee Jeong Ho, Tae Hyun-Jin, Cho Jeong-Hwi, Kim Kyunghwa
College of Veterinary Medicine and Bio-safety Research Institute, Jeonbuk National University, Iksan, 54596, South Korea.
Department of Emergency Medicine of Jeonbuk National University Medical School, Jeonbuk National University Hospital, Jeonju, 54907, South Korea; Research Institute of Clinical Medicine of Jeonbuk National University and Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, South Korea.
J Therm Biol. 2020 Dec;94:102761. doi: 10.1016/j.jtherbio.2020.102761. Epub 2020 Oct 13.
Cardiac arrest (CA) is a leading cause of mortality worldwide. Most of post-resuscitation related deaths are due to post-cardiac arrest syndrome (PCAS). After cardiopulmonary resuscitation (CPR), return of spontaneous circulation (ROSC) leads to renal ischemia-reperfusion injury, also known as PCAS. Many studies have focused on brain and heart injuries after ROSC, but renal failure has largely been ignored. Therefore, we investigated the protective effects of therapeutic hypothermia (TH) on asphyxial CA-induced renal injury in rats. Thirty rats were randomly divided into five groups: 1) the control group (sham); 2) the normothermic CA (nor.); 3) a normothermic CA group that received TH immediately within 2 h after CPR (Hypo. 2 hrs); 4) a normothermic CA group that received TH within 4 h after CPR (Hypo. 4 hrs); and 5) a normothermia CA group that received TH within 6 h after CPR (Hypo. 6 h). One day after CPR, all rats were sacrificed. Compared with the normothermic CA group, the TH groups demonstrated significantly increased survival rate (P < 0.05); decreased serum blood urea nitrogen, creatinine, and lactate dehydrogenase levels; and lower histological damage degree and malondialdehyde concentration in their renal tissue. Terminal deoxynucleotidyl transferase dUTP nick end labeling stain revealed that the number of apoptotic cells significantly decreased after 4 h and 6 h of TH compared to the results seen in the normothermic CA group. Moreover, TH downregulated the expression of cyclooxygenase-2 in the renal cortex compared to the normothermic CA group one day after CPR. These results suggest that TH exerts anti-apoptotic, anti-inflammatory, and anti-oxidative effects immediately after ROSC that protect against renal injury.
心脏骤停(CA)是全球范围内主要的死亡原因。大多数复苏后相关死亡是由于心脏骤停后综合征(PCAS)。心肺复苏(CPR)后,自主循环恢复(ROSC)会导致肾缺血再灌注损伤,也称为PCAS。许多研究聚焦于ROSC后的脑和心脏损伤,但肾衰竭在很大程度上被忽视了。因此,我们研究了治疗性低温(TH)对窒息性CA诱导的大鼠肾损伤的保护作用。30只大鼠被随机分为五组:1)对照组(假手术组);2)常温CA组(常温);3)CPR后2小时内立即接受TH的常温CA组(低温2小时);4)CPR后4小时内接受TH的常温CA组(低温4小时);5)CPR后6小时内接受TH的常温CA组(低温6小时)。CPR后一天,所有大鼠均被处死。与常温CA组相比,TH组的存活率显著提高(P<0.05);血清血尿素氮、肌酐和乳酸脱氢酶水平降低;肾组织的组织学损伤程度和丙二醛浓度降低。末端脱氧核苷酸转移酶dUTP缺口末端标记染色显示,与常温CA组相比,TH处理4小时和6小时后凋亡细胞数量显著减少。此外,与CPR后一天的常温CA组相比,TH下调了肾皮质中环氧合酶-2的表达。这些结果表明,TH在ROSC后立即发挥抗凋亡、抗炎和抗氧化作用,从而预防肾损伤。