ABSTRACT
Objective To investigate the effect of Ⅲ-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment.Methods The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats.Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group,therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group,differentiated by 24 hours and 48 hours after ROSC.Each group had 10 rats at each time point.The anal temperature in the normothermia group was maintained at (37.0 ± 0.2) ℃,and the rats in the hypothermia group were given cooling treatment immediately after ROSC,and the target rectal temperature was 32-34 ℃.In the 3-MA pretreatment group,10 mmol/L 3-MA 5 μL was injected into the ventricle 20 minutes before asphyxia,and other groups were given the same amount of normal saline.Ten rats without CPR were included in Sham group only received anesthesia and catheterization.The rats were sacrificed at 24 hours and 48 hours after ROSC respectively,and the brain tissues were harvested,the brain water content (BWC) was measured by dry-wet weight method.Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3),apoptosis related proteins Bcl-2 and caspase-3,and the Ⅲ-type PI3K pathway proteins Vps34 and Atgl4.Ultrastructural changes in brain tissue were observed with transmission electron microscope.Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC.Results Compared with Sham group,the cortex at 24 hours after ROSC in normothermic group showed obvious edema,apeptosis and autophagy began to appear under transmission electron microscope,and the expressions of autophagy,apoptosis and Ⅲ-type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner,and the neurological function at 48 hours after ROSC was significantly damaged.After hypothermia intervention,brain edema of rats was significantly reduced,no obvious apoptosis was found,but autophagy was increased,the expressions of autophagy-related proteins Vps34,Atg14 and Ⅲ-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH:0.25±0.03 vs.0.15±0.04,Atg14/GAPDH:0.12±0.03 vs.0.05±0.04,Beclin-1/GAPDH:0.060±0.002 vs.0.018±0.002,LC3-Ⅱ/GAPDH:0.160±0.010 vs.0.050± 0.010,all P ＜ 0.05),the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH:0.05±0.03 vs.0.20±0.04,caspase-3/GAPDH:0.050±0.002 vs.0.140±0.015,both P ＜ 0.05),neurological function was significantly improved (NDS:157±85 vs.343± 198,P ＜ 0.05).Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues.The expressions of Vps34,Atg14,Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothennia group (Vps34/GAPDH:0.18±0.03 vs.0.25±0.03,Atg44/GAPDH:0.07±0.04 vs.0.12±0.03,Beclin-1/GAPDH:0.015±0.003 vs.0.060±0.002,LC3-Ⅱ/GAPDH:0.045±0.030 vs.0.160±0.010,all P ＜ 0.05),the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH:0.15±0.04 vs.0.05±0.03,caspase-3/GAPDH:0.120±0.015 vs.0.050±0.002,both P ＜ 0.05),and NDS score was significantly increased (341±208 vs.157±85,P ＜ 0.05).Conclusion Hypothermia treatment reduced brain edema and ameliorated brain function after CPR,which might be related to increase autophagy and inhibit apoptosis adjustment by activating Ⅲ-type PI3K pathway.
ABSTRACT
Objective To study the clinical value of brain natriuretic peptide (BNP) and soluble urokinase plasminogen activator receptor (suPAR) in the diagnosis and prognosis of bloodstream infection.Methods Totally 165 patients suspected of bloodstream infection admitted in intensive care unit (ICU) of the Second Hospital Affiliated to Suzhou University were enrolled in this study.According to the diagnosis standard of bloodstream inflection,patients were divided into the bloodstream infection group and non-bloodstream infection group.According to the prognosis of the patients,the bloodstream infection group was further divided into the survival group and the death group.Serum levels of suPAR,BNP,CRP,PCT,and chronic health evaluation Ⅱ acute physiology score (APACHE Ⅱ),and mortality of the patients were analyzed,and the possible relation of the above indexes between the two groups were compared.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of suPAR,BNP,CRP,PCT,and APACHE Ⅱ score in the bloodstream infection patients was determined.Results Serum levels of suPAR,BNP,CRP,PCT and APACHE Ⅱ score in the bloodstream infection group were higher than those in the non-bloodstream infection group (P＜0.05);Serum levels of suPAR,BNP,CRP,PCT and APACHE Ⅱ score in the death group were higher than those in the survival group (P＜0.05).There was a positive correlation between serum suPAR,BNP,PCT and APHCHE Ⅱ] score in patients of bloodstream infection(r=0.503,0.548,0.781,all P＜0.05).The levels of suPAR,BNP,PCT and APACHE Ⅱ in the patients of blood stream infection were related to significant the prognosis (P＜0.05).And these indexes can provide good evaluation on the prognosis of the patients.Conclusion Detection of serum suPAR,BNP can evaluate the severity of bloodstream infection and preliminarily determine the prognosis of patients with bloodstream infection.Therefore,the method is worth applying in the clinical field.
ABSTRACT
Objective To evaluate the effects of therapeutic hypothermia on both neurological status and survival rate in patients after cardiac arrest.Methods The data were searched from MEDLINE,PubMed,EMBASE,Cochrane Library,Wanfang database,CNKI and CBM.The randomized and controlled trials were selected for evaluating the main outcomes of neurological status and survival rate in patients after cardiac arrest.Meta-analysis was carried out by using Review Manger 5.0 software.The results were expressed in risk ratio (RR) for dichotomous outcomes data with 95％ confidence intervals (CI),and P ＜ 0.05 was considered to be significant.Results Eight randomized controlled clinical trials with a total of 1 512 patients met our inclusion criteria.The overall risk ratio of favorable neurological status was 1.34 (95％ CI:1.01-1.78,P ＜0.05) and of survival rate was 1.09 (95％ CI:0.98-1.20,P ＞0.05) with therapeutic hypothermia compared with controls,however,when the applications of conventional cooling trials were analyzed,the risk ratio was 1.51 (95％ CI:1.22-1.87,P ＜0.01) and 1.36 (95％CI:1.13 -1.63,P ＜ 0.01),respectively.Conclusions Patients treated with therapeutic hypothermia after cardiac arrest had more favorable neurological status compared with the controls.There was no benefit of therapeutic hypothermia to survival rate identified.Compare with conventional cooling methods,the therapeutic hypothermia could improve neurological status and survival rate in patients after cardiac arrest.