Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice  

作　　者：Li Xu Qing Zhang Qing-Song Zhang Qian Li Ji-Yuan Han Peng Sun 

机构地区：[1]Department of Emergency,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China [2]Department of Anesthesia,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China [3]Department of Urology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China [4]Department of Emergency,Wuhan First Hospital,Wuhan,Hubei 430022,China

出　　处：《Chinese Medical Journal》2015年第19期2646-2651,共6页中华医学杂志（英文版）

基　　金：This study was funded by the grants from the National Nature Science Foundation of China （No. 81201444, No. 81101401） and should be attributed to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

摘　　要：Background：Toll-like receptor 4 （TLR4） is a crucial receptor in the innate immune system and noninfectious immune responses.It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion （I/R） injury.However,the role of TLR4 in the process of I/R injury after cardiac arrest （CA） and cardiopulmonary resuscitation （CPR） is still unknown.In this study,we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.Methods：A model of potassium-induced CA was performed on TLR4-mutant mice （C3H/HeJ） and wild-type mice （C3H/HeN）.After 3 min of untreated CA,resuscitation was attempted with chest compression,ventilation,and intravenous epinephrine.Behavioral tests were performed on mice on day 3 after CPR.The morphological changes in hippocampal neurons were assessed by light and electron microscopy.Expressions of TLR4 and intercellular adhesion molecule-1 （ICAM-l） were detected by Western blot.Levels of tumor necrosis factor-α （TNF-α） and myeloperoxidase （MPO） were measured with enzyme-linked immunosorbent assay （ELISA）.Results：On day 3 after resuscitation the overall mortality was 33.33％ in C3H/HeJ group compared with 53.33％ in C3H/HeN group （P ＜ 0.05）.And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test （P ＜ 0.05）.Meanwhile,the percentage of nonviable neurons was 2 1.16％ in C3 H/HeJ group compared with 53.11％ in C3H/HeN group （P ＜ 0.05）.And there were significantly lower levels ofhippocampal TNF-α and MPO in C3H/HeJ mice （TNF-α：6.85±1.19 ng/mL,MPO：0.33±0.11 U/g） than C3 H/HeN mice （TNF-α：11.36±2.12 ng/mL,MPO：0.54±0.17 U/g） （all P ＜ 0.01）.CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group.However,the expression ofICAM-l was much lower in C3H/HeJ group than in C3H/HeN group after CPR （P ＜ 0.01）.Conclusion：TLR4 signaling is involved in brain damage and in Background：Toll-like receptor 4 （TLR4） is a crucial receptor in the innate immune system and noninfectious immune responses.It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion （I/R） injury.However,the role of TLR4 in the process of I/R injury after cardiac arrest （CA） and cardiopulmonary resuscitation （CPR） is still unknown.In this study,we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.Methods：A model of potassium-induced CA was performed on TLR4-mutant mice （C3H/HeJ） and wild-type mice （C3H/HeN）.After 3 min of untreated CA,resuscitation was attempted with chest compression,ventilation,and intravenous epinephrine.Behavioral tests were performed on mice on day 3 after CPR.The morphological changes in hippocampal neurons were assessed by light and electron microscopy.Expressions of TLR4 and intercellular adhesion molecule-1 （ICAM-l） were detected by Western blot.Levels of tumor necrosis factor-α （TNF-α） and myeloperoxidase （MPO） were measured with enzyme-linked immunosorbent assay （ELISA）.Results：On day 3 after resuscitation the overall mortality was 33.33％ in C3H/HeJ group compared with 53.33％ in C3H/HeN group （P ＜ 0.05）.And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test （P ＜ 0.05）.Meanwhile,the percentage of nonviable neurons was 2 1.16％ in C3 H/HeJ group compared with 53.11％ in C3H/HeN group （P ＜ 0.05）.And there were significantly lower levels ofhippocampal TNF-α and MPO in C3H/HeJ mice （TNF-α：6.85±1.19 ng/mL,MPO：0.33±0.11 U/g） than C3 H/HeN mice （TNF-α：11.36±2.12 ng/mL,MPO：0.54±0.17 U/g） （all P ＜ 0.01）.CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group.However,the expression ofICAM-l was much lower in C3H/HeJ group than in C3H/HeN group after CPR （P ＜ 0.01）.Conclusion：TLR4 signaling is involved in brain damage and in

关 键 词：Cardiac Arrest Cardiopulmonary Resuscitation Cerebral Injury Toll-like Receptor 4 

分 类 号：Q782[生物学—分子生物学] Q954