Protection of intestinal immune barrier against ischemia/reperfusion injury in a swine model using anisodamine hydrobromide

Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection.

摘要 肠缺血再灌注（I/R）可引发肠道屏障损伤与细菌移位。本研究探讨氢溴酸山莨菪碱（AH）对心脏骤停（CA）后心肺复苏（CPR）所致肠I/R损伤的保护作用。成功实施CPR后，将小型猪随机分为两组（n=8）：生理盐水组与AH给药组（4 mg/kg），分别经中心静脉注射生理盐水或AH；假手术组（n=8）仅开展相同操作但不诱发心室颤动。于自主循环恢复（ROSC）后不同时间点（0、0.5、1、2、4及6 h）采集血清样本，并于ROSC后6 h采集肠相关淋巴组织（GALTs）样本，检测干扰素γ（IFN-γ）与白细胞介素4（IL-4）水平，以评估辅助性T细胞1型（Th1）与辅助性T细胞2型（Th2）的比例变化。此外，检测GALTs的细菌培养阳性率以评价细菌移位情况。结果显示，AH给药可显著改善CPR后异常的动脉血气与血流动力学指标，同时减轻肠道大体及形态学损伤；AH给药还可显著升高血清与GALTs中的IFN-γ水平并降低IL-4水平。进一步研究发现，AH给药可显著降低GALTs的细菌培养阳性率。综上，AH给药可缓解肠I/R所致的免疫抑制，保护肠道免疫屏障抵御细菌移位，从而降低继发性肠道感染风险。