Department of Emergency Medicine, Zhejiang Hospital, Hangzhou, China.
Shock. 2023 May 1;59(5):803-809. doi: 10.1097/SHK.0000000000002107. Epub 2023 Feb 28.
Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 10 6 /kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.
心脏骤停（CA）和复苏引发的全身缺血再灌注常导致复苏后多器官损伤。间充质干细胞（MSCs）已被证明是治疗肾和肠局部缺血再灌注损伤的一种有前途的方法。本研究旨在探讨 MSCs 对猪 CA 模型心肺复苏（CPR）后肾和肠损伤的影响。
22 只雄性猪随机分为假手术（n = 6）、CA/CPR（n = 8）和 CA/CPR+MSC（n = 8）组。MSCs 从人胚胎干细胞中分化而来，在 CA/CPR 前 1.5 天和 3 天以 2.5×10 6 /kg 的剂量静脉给药。通过未经处理的 CA 8 分钟和随后的 CPR 8 分钟建立实验模型。在复苏后 1、2、4 和 24 小时，根据血清肌酐、血清尿素氮、肠脂肪酸结合蛋白和二胺氧化酶水平评估肾和肠损伤。实验结束时，通过肾和肠组织中的细胞凋亡和铁死亡确定病理损伤。
在 CPR 期间，CA/CPR 组中有 5 只猪和 CA/CPR+MSC 组中有 7 只猪成功复苏。复苏后，CA/CPR 和 CA/CPR+MSC 组血清肌酐、血清尿素氮、肠脂肪酸结合蛋白和二胺氧化酶水平均明显高于假手术组。然而，与 CA/CPR 组相比，MSC 给药显著降低了肾和肠损伤生物标志物的水平。在 CA/CPR 和 CA/CPR+MSC 组中，复苏后肾和肠组织中观察到细胞凋亡和铁死亡，其表现为凋亡细胞、铁沉积、脂质过氧化、抗氧化剂和铁死亡相关蛋白的水平。然而，在 CA/CPR+MSC 组中，两者均明显轻于 CA/CPR 组。
在猪 CA 模型中，MSC 给药通过抑制细胞凋亡和铁死亡，对复苏后肾和肠损伤有缓解作用。
