Hua Tianfeng, Lu Zongqing, Wang Minjie, Zhang Yijun, Chu Yuqian, Liu Yue, Xiao Wenyan, Zhou Wuming, Cui Xuanxuan, Shi Wei, Zhang Jin, Yang Min
The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, 230601, PR China.
Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, 230601, PR China.
Heliyon. 2024 May 23;10(11):e31377. doi: 10.1016/j.heliyon.2024.e31377. eCollection 2024 Jun 15.
Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing.
Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP 'were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed.
SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group.
SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.
参附（SF）注射液是一种传统中药，可改善心源性休克和感染性休克中的微循环。本研究旨在探讨参附注射液对严重失血性休克（SHS）及复苏后肠道缺血再灌注（I/R）损伤的治疗潜力。此外，我们还研究了最佳给药时机。
将24只雄性SD大鼠随机分为四组：假手术组（sham，n = 6）、对照组（n = 6）、参附注射液组（SF，n = 6）和参附注射液延迟给药组（SF-delay，n = 6）。在SHS及复苏模型中，通过放血使大鼠在1小时内平均动脉压（MAP）降至40±5 mmHg，然后维持40分钟；记录心率、MAP，分析微循环指标[德贝克尔评分、灌注小血管密度（PSVD）、总血管密度（TVD）、微循环血流指数评分（MFI）、血流异质性指数（HI）]。检测血气指标，采用酶联免疫吸附测定法（ELISA）测定白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、二胺氧化酶（DAO）、丙二醛（MDA）；采用蛋白质免疫印迹法检测紧密连接蛋白-1（ZO-1）和闭合蛋白-1（claudin-1）。此外，还对肠黏膜组织进行苏木精-伊红（HE）和过碘酸希夫（PAS）染色病理切片检查。
参附注射液可提高MAP，减轻与低灌注相关的代谢性酸中毒程度，并改善I/R损伤后的肠道微循环密度和灌注质量。与对照组相比，参附注射液组肠组织中DAO、MDA的表达及血浆IL-6、TNF-α水平显著降低。参附注射液组中ZO-1和claudin-1的浓度也更高。此外，HE和PAS染色结果还显示，参附注射液可减轻黏膜损伤并维持结构。在SF-delay组中，肠组织损伤程度介于对照组和参附注射液组之间。
参附注射液可保护肠道免受SHS及复苏诱导的I/R损伤，其机制可能是通过改善肠道微循环、减少炎症因子过度释放及增加肠黏膜通透性。此外，在初始复苏阶段给药时保护作用更明显。
