Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocam...Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.展开更多
Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain un...Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016(approval No. 2016079).展开更多
BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equal...BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.展开更多
BACKGROUND:Good neurological outcome after cardiac arrest(CA) is hard to achieve for clinicians.Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial.This study aimed to assess th...BACKGROUND:Good neurological outcome after cardiac arrest(CA) is hard to achieve for clinicians.Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial.This study aimed to assess the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from CA using a meta-analysis.METHODS:We searched the MEDLINE(1966 to April 2012),OVID(1980 to April 2012),EMBASE(1980 to April 2012),Chinese bio-medical literature & retrieval system(CBM)(1978 to April 2012),Chinese medical current contents(CMCC)(1995 to April 2012),and Chinese medical academic conference(CMAC)(1994 to April 2012).Studies were included if 1) the study design was a randomized controlled trial(RCT);2) the study population included patients successfully resuscitated from CA,and received either standard post-resuscitation care with normothermia or mild hypothermia;3) the study provided data on good neurologic outcome and survival to hospital discharge.Relative risk(RR) and 95%confidence interval(CI) were used to pool the effect.RESULTS:The study included four RCTs with a total of 417 patients successfully resuscitated from CA.Compared to standard post-resuscitation care with normothermia,patients in the hypothermia group were more likely to have good neurologic outcome(RR=1.43,95%CI 1.14-1.80,P=0.002) and were more likely to survive to hospital discharge(RR=1.32,95%CI 1.08-1.63,P=0.008).There was no significant difference in adverse events between the normothermia and hypothermia groups(P>0.05),nor heterogeneity and publication bias.CONCLUSION:Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from CA.展开更多
BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation...BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation(CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fi brillation(VF) versus asphyxial cardiac arrest.METHODS: Sixty-two male Sprague-Dawley(SD) rats were randomly divided into an asphyxial group(n=32) and a VF group(n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly lower than those in the asphyxial group(12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation(ROSC), compared with those in rats without ROSC(16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly higher than those in rats without ROSC(20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic(ROC) curves of PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.展开更多
基金supported by the Fujian Provincial Health Technology Project of China,No.2018-CX-16Fujian Provincial Hospital Flint Fund Project,No.2020HSJJ17(both to SRL).
文摘Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.
基金supported by the Natural Science Foundation of Fujian Province of China,No.2015J01375(to QML)Fujian Provincial Hospital Foundation of China,No.2014070(to QML)
文摘Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016(approval No. 2016079).
文摘BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.
文摘BACKGROUND:Good neurological outcome after cardiac arrest(CA) is hard to achieve for clinicians.Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial.This study aimed to assess the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from CA using a meta-analysis.METHODS:We searched the MEDLINE(1966 to April 2012),OVID(1980 to April 2012),EMBASE(1980 to April 2012),Chinese bio-medical literature & retrieval system(CBM)(1978 to April 2012),Chinese medical current contents(CMCC)(1995 to April 2012),and Chinese medical academic conference(CMAC)(1994 to April 2012).Studies were included if 1) the study design was a randomized controlled trial(RCT);2) the study population included patients successfully resuscitated from CA,and received either standard post-resuscitation care with normothermia or mild hypothermia;3) the study provided data on good neurologic outcome and survival to hospital discharge.Relative risk(RR) and 95%confidence interval(CI) were used to pool the effect.RESULTS:The study included four RCTs with a total of 417 patients successfully resuscitated from CA.Compared to standard post-resuscitation care with normothermia,patients in the hypothermia group were more likely to have good neurologic outcome(RR=1.43,95%CI 1.14-1.80,P=0.002) and were more likely to survive to hospital discharge(RR=1.32,95%CI 1.08-1.63,P=0.008).There was no significant difference in adverse events between the normothermia and hypothermia groups(P>0.05),nor heterogeneity and publication bias.CONCLUSION:Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from CA.
基金supported in part by grants from the National Natural Science Foundation of China(30700303)the National Clinical Key Subject Construction Project
文摘BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation(CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fi brillation(VF) versus asphyxial cardiac arrest.METHODS: Sixty-two male Sprague-Dawley(SD) rats were randomly divided into an asphyxial group(n=32) and a VF group(n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly lower than those in the asphyxial group(12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation(ROSC), compared with those in rats without ROSC(16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly higher than those in rats without ROSC(20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic(ROC) curves of PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.
