Department of anesthesiology, Zhongda Hospital Southeast University, Nanjing 210000, Jiangsu, China.
Department of anesthesiology, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Shock. 2023 Jun 1;59(6):892-901. doi: 10.1097/SHK.0000000000002113. Epub 2023 Mar 20.
Background : Systemic inflammation acts as a contributor to neurologic deficits after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracellular cold-inducible RNA-binding, protein (CIRP) has been demonstrated to be responsible in part for the inflammation through binding to toll-like receptor 4 (TLR4) after cerebral ischemia. The short peptide C23 derived from CIRP has a high affinity for TLR4, we hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. Methods : Adult male SD rats in experimental groups were subjected to 5 min of CA followed by resuscitation. C23 peptide (8 mg/kg) or normal saline was injected intraperitoneally at the beginning of the return of spontaneous circulation (ROSC). Results : The expressions of CIRP, TNF-α, IL-6, and IL-1β in serum and brain tissues were significantly increased at 24 h after ROSC ( P < 0.05). C23 treatment could markedly decrease the expressions of TNF-α, IL-6, and IL-1β in serum ( P < 0.05). Besides, it can decrease the expressions of TLR4, TNF-α, IL-6, and IL-1β in the cortex and hippocampus and inhibit the colocalization of CIRP and TLR4 ( P < 0.05). In addition, C23 treatment can reduce the apoptosis of hippocampus neurons ( P < 0.05). Finally, the rats in the C23 group have improved survival rate and neurological prognosis ( P < 0.05). Conclusions: These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-CA syndrome.
全身性炎症是心脏骤停（CA）和心肺复苏（CPR）后神经功能缺损的一个促成因素。已证实细胞外冷诱导 RNA 结合蛋白（CIRP）通过与脑缺血后的 toll 样受体 4（TLR4）结合，在部分程度上导致炎症。CIRP 的短肽 C23 与 TLR4 具有高亲和力，我们假设 C23 通过阻断 CIRP 与 TLR4 的结合来减少 CA/CPR 后的全身炎症。方法：实验各组的成年雄性 SD 大鼠接受 5 分钟的 CA 后再进行复苏。在自主循环恢复（ROSC）开始时，腹腔内注射 C23 肽（8mg/kg）或生理盐水。结果：ROSC 后 24 小时，血清和脑组织中 CIRP、TNF-α、IL-6 和 IL-1β 的表达明显增加（P<0.05）。C23 治疗可显著降低血清中 TNF-α、IL-6 和 IL-1β 的表达（P<0.05）。此外，它可以降低皮质和海马中 TLR4、TNF-α、IL-6 和 IL-1β 的表达，并抑制 CIRP 和 TLR4 的共定位（P<0.05）。此外，C23 治疗可以减少海马神经元的凋亡（P<0.05）。最后，C23 组的大鼠存活率和神经预后得到改善（P<0.05）。结论：这些发现表明 C23 可以减轻全身炎症，并有可能开发为治疗 CA 后综合征的一种潜在疗法。
