Protective Effects And Mechanisms Of Xuezhikang On The Brain Injury After Cardiopulmonary Resuscitation In Rats

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 main 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.Methods:An animal model of cardiac arrest in SD rats was established by modified percutaneous epicardial electrical stimulation.Rats were divided into 5 groups randomly:(1)Sham group;(2)CPR group;(3)XZK-L group;(4)XZK-H group;(5)Lova group.Rats were treated with low-dose XZK(XZK-L,20mg/kg/d),high-dose XZK(XZK-H,200mg/kg/d)and lovastatin by gavage once daily for 2 weeks before CA/CPR.The serum levels of TNF-α,IL-6 and IL-1β were detected by ELISA method at 1,4,and 72 hours after CA/CPR.Quantitative real-time PCR was used to detect the mRNA expression of inflammatory factors in hippocampus at 72 hours after resuscitation.The survival rate and neurological deficit score(NDS)were evaluated at 72 hours after CA/CPR,and expression of TLR4,phosphorylated NF-κB and TNF-α in hippocampal tissues were detected by immunofluorescence and Western blot.Results: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 hippocampus.Both low-dose and high-dose XZK treatment inhibited the expressions of these inflammatory factors(P<0.05).In addition,XZK treatment reduced the number of defibrillation required and shortened the duration of CPR,and also improved neurological function,and 72-hour survival rate in rats(P<0.05).At the same time,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.Conclusions:These results indicated that XZK protected against brain injury after CA/CPR in rats.The mechanisms underlying protective effects of XZK may be related to suppressing CA/CPR-induced inflammatory response by inhibiting TLR4/NF-κB signaling pathway.