Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Intensive Care Unit, Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430022, China.
Biomed Pharmacother. 2019 Jun;114:108817. doi: 10.1016/j.biopha.2019.108817. Epub 2019 Apr 4.
BACKGROUND/AIMS: Xuezhikang (XZK), a red yeast rice extract with lipid-lowering effect, contains a family of naturally statins, such as lovastatin. In recent years, its effect beyond the regulation of lipids has also been received increasing attention. Therefore, the purpose of this study was to explore the protective effects and possible molecular mechanisms of XZK on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and to investigate whether it has a dose-dependent effect and the difference with lovastatin.
Rats were treated with low-dose XZK (XZK-L, 20 mg/kg/d), high-dose XZK (XZK-H, 200 mg/kg/d) and lovastatin by gavage once daily for 2 weeks before CA. The levels of TNF-α, IL-6 and IL-1β were evaluated at 1, 4, and 72 h post-CA/CPR. The survival rate, neurological deficit score (NDS), and expression of TLR4, phosphorylated NF-κB and TNF-α in hippocampal tissues were evaluated at 72 h post-CA/CPR.
CA/CPR induced a significant increase in serum TNF-α, IL-6 and IL-1β, as well as increased expressions of TLR4, phosphorylated NF-κB and TNF-α in the hippocampus. Both low-dose and high-dose XZK treatment inhibited the expression of these inflammatory cytokines. In addition, it reduced the number of defibrillations and shortened the duration of CPR required for return of spontaneous circulation (ROSC). XZK treatment also improved neurological function and 72-hour survival rate in rats. However, high-dose XZK was superior to lovastatin in the suppression of IL-1β mRNA level and TNF-α protein level in hippocampal tissue after CPR. There were no significant differences observed among high-dose XZK, low-dose XZK and lovastatin groups in other respects.
These results indicated that XZK had a protective effect against brain injury post-CA/CPR. The mechanisms underlying the protective effects of XZK may be related to the suppressing of CA/CPR-induced inflammatory response through the inhibiting TLR4/NF-κB signaling pathway.
背景/目的：脂必泰（XZK）是一种具有降脂作用的红曲提取物，含有洛伐他汀等天然他汀家族。近年来，其降脂作用以外的作用也受到越来越多的关注。因此，本研究旨在探讨 XZK 对心肺复苏后心脏骤停（CA）和心肺复苏（CPR）脑损伤的保护作用及其可能的分子机制，并探讨其是否具有剂量依赖性及其与洛伐他汀的差异。
CA 前 2 周，大鼠每日灌胃低剂量 XZK（XZK-L，20mg/kg/d）、高剂量 XZK（XZK-H，200mg/kg/d）和洛伐他汀。CA/CPR 后 1、4 和 72h 评估 TNF-α、IL-6 和 IL-1β 水平。CA/CPR 后 72h 评估存活率、神经功能缺损评分（NDS）以及海马组织 TLR4、磷酸化 NF-κB 和 TNF-α的表达。
CA/CPR 导致血清 TNF-α、IL-6 和 IL-1β 显著增加，海马 TLR4、磷酸化 NF-κB 和 TNF-α表达增加。低剂量和高剂量 XZK 治疗均抑制了这些炎症细胞因子的表达。此外，它减少了除颤次数，并缩短了自主循环恢复（ROSC）所需的 CPR 持续时间。XZK 治疗还改善了大鼠的神经功能和 72 小时存活率。然而，与洛伐他汀相比，高剂量 XZK 能更好地抑制 CPR 后海马组织中 IL-1βmRNA 水平和 TNF-α 蛋白水平。在其他方面，高剂量 XZK、低剂量 XZK 和洛伐他汀组之间没有观察到显著差异。
这些结果表明 XZK 对 CA/CPR 后脑损伤具有保护作用。XZK 的保护作用机制可能与通过抑制 TLR4/NF-κB 信号通路抑制 CA/CPR 诱导的炎症反应有关。
