Xuezhikang improves the outcomes of cardiopulmonary resuscitation in rats by suppressing the inflammation response through TLR4/NF-κB pathway

• Published in: Biomedicine & pharmacotherapy 2019-06, Vol.114, p.108817-108817, Article 108817
• Main Authors: Liang, Licai, Shao, Weijing, Shu, Tingting, Zhang, Yuhan, Xu, Shuang, Guo, Lang, Zhou, Yuran, Huang, He, Sun, Peng
• Format: Article
• Language: English
• Subjects: Cardiac arrest; Cardiopulmonary resuscitation; Inflammation; NF-κB; TLR4; Xuezhikang
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.108817

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.