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Objective:To explore the effects and the possible mechanism of bone marrow mesenchymal stem cell (BMMSC) transplantation on apoptosis in rats cerebral cortex after cardiac arrest/cardiopulmonary resuscitation (CA/CPR).Methods:The BMMSC of 2 Sprague-Dawley (SD) rats aged 4-5weeks was extracted, and the 3rd passage was used in experimental study. Eighteen Sprague-Dawley (SD) rats were divided into sham group, model group (CA/CPR group) and intervention group (BMMSC group) according to random number table method, with 6 rats in each group. CPR was performed 6 minutes after asphyxia induced CA. In sham group, CA was not induced except performing general surgical procedure. At 1 hour after return of spontaneous circulation (ROSC), 0.5 mL phosphate buffered saline (PBS) was injected through tail vein in CA/CPR group. 2×10 9/L green fluorescence protein (GFP)-labeled BMMSC was injected through tail vein 1 hour after ROSC in BMMSC group. Neurological deficit score (NDS) were assessed in every group at 72 hours after CPR. Serum S100 calcium binding protein B (S100B) levels were assayed by enzyme linked immunosorbent assay (ELISA). Distribution of BMMSC in brain was observed under a fluorescent microscope. Apoptosis rate in cerebral cortex was assayed by TdT-mediated dUTP nick-end labeling (TUNEL). Western blotting was performed to measure the expression levels of active aspartic acid specific cysteine proteinase (caspase-8 and caspase-9) in cerebral cortex. Results:At 3 days after CPR, compared with sham group, the apoptosis of cerebral cortex cells was increased and brain damage was obvious, NDS score was decreased significantly (56.6±5.5 vs. 80.0±0.0, P < 0.05), and serum S100B was increased markedly (ng/L: 45.1±4.7 vs. 19.1±1.4, P < 0.05), apoptosis rate of cerebral cortex cells increased significantly [(52.9±11.8)% vs. (10.1±1.5)%, P < 0.05], the level of active caspase-8 expression in cerebral cortex was significantly higher (caspase-8/GAPDH: 0.689±0.047 vs. 0.330±0.108, P < 0.05), and there was no significant difference in active caspase-9 protein expression (caspase-9/GAPDH: 0.428±0.014 vs. 0.426±0.021, P > 0.05) in CA/CPR group. After BMMSC transplantation, GFP-labeled BMMSC were primarily detected in cerebral cortex, compared with CA/CPR group, the apoptosis of cerebral cortex cells and brain injury were significantly improved in BMMSC group, NDS score increased significantly (70.6±2.1 vs. 56.6±5.5, P < 0.05), serum S100B levels in BMMSC group were lower (ng/L: 32.0±3.2 vs. 45.1±4.7, P < 0.05), apoptosis rate of cerebral cortex cells decreased significantly [(31.1±3.4)% vs. (52.9±11.8)%, P < 0.05], and the active caspase-8 expression in cerebral cortex in BMMSC group was significantly decreased (caspase-8/GAPDH: 0.427±0.067 vs. 0.689±0.047, P < 0.05). The active caspase-9 expression in cerebral cortex in BMMSC group and CA/CPR group were not significantly different (caspase-9/GAPDH: 0.431±0.022 vs. 0.428±0.014, P > 0.05). Conclusion:BMMSC transplantation can alleviate rat brain damage after CA/CPR possibly by inhibiting the death receptor mediated apoptotic pathway to inhibit the apoptosis of brain cells.
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Objective:To explore the protective effects of bradykinin postconditioning on cardiopulmonary resuscitation (CPR) rats, and to assess the underlying mechanisms.Methods:Forty-eight adult male Sprague-Dawley (SD) rats were randomly divided into four groups according to random number table: Sham operation group, cardiac arrest (CA) group, bradykinin treatment (BK) group, and AMP-activated protein kinase (AMPK) inhibitor Compound C+ bradykinin treatment (CP+BK) group, finally, 8 rats in each group were taken for follow-up experiment. CA was induced by asphyxia. Rats in the Sham group received arteriovenous catheterization, endotracheal intubation, and mechanical ventilation, without CA. Compound C (250 μg/kg) was intraperitoneally injected in CP+BK group 30 minutes before CA, and the same volume of dimethyl sulfoxide (DMSO) was given in the remaining groups. Bradykinin (150 μg/kg) was intraperitoneally injected in BK group and CP+BK group 48 hours after restoration of spontaneous circulation (ROSC), and same volume of saline was given in the remaining groups. The neural function of rats in each group was evaluated with neurological deficit score (NDS) 72 hours after ROSC. Microtubule-associated protein light chain 3 (LC3) and p62 expressions were detected by immunohistochemistry, autophagosomes were observed by transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL) assay was used to assess apoptosis.Results:Compared with the Sham group, the NDS was decreased (60.75±5.80 vs. 80.00±0.00, P < 0.01), the expression levels of LC3 and p62 elevated [LC3 ( A value): 1.04±0.64 vs. 0.40±0.14, p62 ( A value): 2.75±0.57 vs. 0.36±0.12, both P < 0.05], the number of autophagosomes and apoptotic cells increased in the CA group [(39.00±8.00)% vs. (3.87±1.90)%, P < 0.05]. Compared with the CA group, the NDS (67.75±6.32 vs. 60.75±5.80, P < 0.05), the expression of LC3 ( A value: 1.60±0.34 vs. 1.04±0.64, P < 0.05), and the number of autophagosomes increased in the BK group, while the expression of p62 and the rate of apoptotic cells reduced [p62 ( A value): 1.51±0.32 vs. 2.75±0.57, apoptotic cells rate: (23.03±1.91)% vs. (39.00±8.00)%, both P < 0.05]. Compared with the BK group, the NDS (59.00±8.19 vs. 67.75±6.32, P < 0.05), the expression of LC3 ( A value: 0.62±0.41 vs. 1.60±0.34, P < 0.05) and the number of autophagosomes declined in the CP+BK group, while the expression of p62 and the rate of apoptotic cells elevated [p62 ( A value): 3.50±0.47 vs. 1.51±0.32, apoptotic cells rate: (44.53±10.15)% vs. (23.03±1.91)%, both P < 0.05]. Conclusion:Bradykinin postconditioning played a neuroprotective role in CPR rats by activating autophagy and reducing apoptosis.
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Objective To investigate the effects of transplantation with different amount of bone marrow mesenchymal stem cells(BMSCs)on osteoporosis in ovariectomized rats.Methods The rat model of osteoporosis was prepared by ovariectom(OVX)and verified after 3 months.A total of 60 female Sprague-Dawley rats were randomly divided into 6 groups(n=10 each).The rats with shamed operation served as a sham-injured control group(sham control group).The 5 ovariectom (OVX) groups with osteoporosis were study groups as follows:(1)the negative therapy group(simple OVX group);(2)the positive therapy group(OVX+ estrogen,E2 group) by intramuscular injection;others were treated with transplantation of BMSCs by tail vein injection in low dose(LS group),middle dose (MS group)and high dose(HS group).At 8,12 and 16 weeks after intervention,body mineral density (BMD)were detected by dual-energy x-ray absorptiometry scans.After 16 weeks of intervention,rat shinbone was obtained and stained by hematoxylin-eosin(HE) staining.Results Compared with the sham control group,simple OVX group showed a reduced total body BMD and the decreased proportion of trabecular bone to bone marrow cavity area (P ＜0.05).The total body BMD and the proportion of trabecular bone to bone marrow cavity area were higher in each BMSCs transplantation groups than in simple OVX group at 8,12,16 weeks after intervention(P ＜0.05),which showed a increased trend in the total body BMD and the proportion with the increased dose of transplantation BMSCs(P＜0.05).Rats in the HS group had highest BMD and best proportion of trabecular bone to bone marrow cavity area among three doses of transplantation BMSCs.Conclusions BMSCs transplantation can significantly improve osteoporosis of ovariectomized rats with an increased total body BMD and higher proportion of trabecular bone to bone marrow cavity area,and better and longer outcomes can be achieved.
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Objective To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of nerve growth factor (NGF) and Caspase-3 in rat hippocampus after cardiac arrest (CA). Methods Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=6), CA group (n=6), and BMSCs group (n=6). CPR was performed on the groups after the induction of asphyxial cardiac arrest. Animals in the BMSCs group or the CA group were respectively injected with a dose of 1×106 BMSCs in 0.5 mL phosphate buffer solution (PBS) or 0.5 mL PBS alone via the vena caudalis 1 h after successful resuscitation. The neurological status after restoration of spontaneous circulation (ROSC) were assessed by modified neurological severity scores (mNSS); serum levels of S100B were assayed, and the expression of NGF and Caspase-3 in hippocampus was detected by immunohistochemistry. Results Compared with the CA group, mNSS and S100B levels were lower in the BMSCs group on the 7th day after ROSC [(0.9±0.3) vs (4.5±0.6), (90.12±4.62) pg/mL vs (182.30±2.58) pg/mL, both P<0.05] with higher expression of NGF and lower expression of Caspase-3 [(11.391±1.297) vs (7.744±1.334), (6.256±1.036) vs (8.506±1.742), both P< 0.05]. Conclusions BMSCs transplantation might improve rat's neurological functions after cardiac arrest, which may be related to up-regulation of NGF expression and down-regulation of Caspase-3 expression.
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Objective To explore the effects of bone marrow mesenchymal stem cells (MSCs) transplantation on receptor-interacting protein kinase 1 (RIP1) and RIP3 in rat brain after cardiac arrest (CA).Methods Sprague Dawley (SD) rats were randomly (random number) divided into sham group (n=8),CA group (n=8) and MSCs group (n=8).Animals were subjected to asphyxial cardiac arrest and followed by cardiopulmonary resuscitation (CPR).In MSCs group or CA group,animals received intravenous injection of 1 × 106 MSCs in 0.5 mL phosphate buffer solution (PBS) or 0.5 mL PBS alone at 1 h after successful resuscitation.Neurological deficit scores (NDS) were assessed at 3 d after CPR.Donor MSCs in brain were detected under a fluorescent microscope.HE staining of brain tissue was performed to observe necrotic neurons.Western blot analysis was performed to measure the levels of RIP1 and RIP3 in brain.Multiple comparisons were made by analysis of variance or Kruskal-Wallis H test.Results At 3 d after CPR,MSCs group demonstrated higher NDS than CA group [72.5(71.5,73.2) vs.63.0(62.5,64.1),Z=3.376,P=0.001].DAPI-labeled MSCs were primarily observed in the cerebral cortex.The percentage of necrotic neurons in MSCs group was significantly lower than that in CA group [(29.6±5.9)％ vs.(57.2±6.4)％,t=8.922,P＜0.01].The levels of RIP1 and RIP3 expression in brain in MSCs group were significantly lower than those in CA group [RIP1:0.227(0.193,0.243) vs.0.599(0.535,0.629),Z=3.151,P=0.001;RIP3:0.217(0.203,0.274) vs.0.543(0.533,0.555),Z=3.361,P=0.001].Conclusion MSCs transplantation improves neurological function after CPR from CA in rats likely associated with inhibiting necroptosis.
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Objective To investigate the changes of diffusion tensor imaging (DTI) in the cerebral white matter of rats with ischemia-reperfusion injury.Methods Adult SD rats were randomly divided into two groups,sham operation group and model group.The model of ischemia reperfusion injury was made by the Koizumi suture method to occlude the middle cerebral artery.Application of Zea-Longa score was carried out to determine the establishment of modeling,and the modified neurological severity score (mNSS) was used to evaluate the neurological deficit of rats.The Rotarod test instrument was used to observe the motor function of rats by using Rotarod fatigue balance signs,and the DTI sequence scanning observation of brain white matter nerve fiber damage was determined by using Brook 7.0T small animal magnetic resonance imaging system.Track Vis software was used to analyze the distribution of cerebral white matter nerve fibers,and the relative number of nerve fibers in the areas of ROI (region of interest,ROI),sensorimotor areas and striatum were calculated.Results The results showed varying degrees of neurological impairment in rats 2 h after cerebral ischemia reperfusion injury,and the Zea-Longa score and the mNSS score were gradually reduced at the 1 d,7 d and 14 d after ischemia reperfusion injury.The time of rats retaining on the rotating rod was shortened at the 7 d and 14 d after ischemia reperfusion injury.At the ischemic lateral,nerve fibers decreased significantly,and the number of sensory nerve fiber connections in the sensorimotor areas to striatum was reduced.Nissl staining showed that the cytoplasm of neurons in the sensorimotor cortex and striatum of the ischemic lateral were disappeared and the Nissl bodies were decreased.Conclusions The nerve fibers of sensory motor cortex connecting to striatum were damaged by ischemia reperfusion injury.
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Objective To investigate the improvement of ischemic hypoxic injury of brain after the transplantation of bone marrow mesenchymal stem cells (BMSCs).Methods Rats were randomly (random number) divided into sham operation group,cardiac arrest group and BMSCs treatment group (n =10 in each group).The model of cardiac arrest was induced by asphyxia.One hour after restoration of spontaneous circulation (ROSC),green fluorescent protein labeled BMSCs were transplanted via tail vein injection.At 3 and 7 days after transplantation,frozen sections of hippocampus was stained with hematoxylin-eosin (HE).The rest of brain tissue was weighed by an electronic balance.Brain water content (％) was calculated as (wet weight-dry weight) / wet weight × 100％.Results ①BMSCs were observed in hippocampus at 3 and 7 days after transplantation under fluorescent microscopy.②Compared with sham operation group and BMSCs treatment group,brain water content in cardiac arrest group was higher (all P ＜ 0.05).HE staining results showed that BMSCs transplantation could lessen hypoxia ischemia damage on brain.Conclusions BMSCs reduced the neurons damage induced by cardiac arrest and promoted neurological function recovery.
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Objective To explore the protective effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) on pulmonary fibrosis induced by paraquat (PQ) in rats.Methods A total of 54 male SD rats were randomly (random number) divided into 3 groups (n =18 in each).Group A (normal control group),group B [PQ + phosphate buffer solution (PBS)],group C (PQ + BMSCs group).Rats in group B and C were induced to get pulmonary fibrosis by intragastric administration of PQ in a dosage of 120 mg/kg.In addition,BMSCs was given to rats in group C by injection in a dose of 1 × 106/mL via the vena caudalis,whereas an equal volume of PBS (1 mL) was given to rats in group B by injection instead.The survival rats in each groups were sacrificed separately at 7 days,14 days and 28 days after administration of PQ.The lower lobe of left lung were taken to observe histopathological changes with HE staining and Masson staining,and the pulmonary fibrosis was scored by using the Szapiel classification of alveolitis.At the same time,the lower lobe of right lung was harvested to detect the hydroxyproline (HYP),TGF-β1 and HGF in lung tissue by using immunohistochemistry.Results The pathological changes in lung tissue of rats were inflammatory change in alveoli space filled with massive amount of exudate obviously in group B at 7 days after exposure to PQ,but in group C,the inflammatory changes were much milder than those in group B.The exudation and edema in lunge alveoli were mitigated in group B at 14 days after exposure to PQ,but pulmonary interstitial fibers were increased.The degree of pulmonary interstitial fibrosis in group C was milder than that in group B.In group B,there were obvious pathological changes including destroyed alveoli septum,enlarged alveoli,thickened alveoli septum and the deposition of collagen fibers,disarranged alveolar structure at 28 days after exposure to PQ.The deposition off collagen fiber was slighter with well observed basic alveolar structure in group C than that in group B.The levels of HYP in lung tissue at different intervals in B group were escalating with time after exposure to PQ,and reached a peak at 28 day,which were significantly higher than those in group A (P ＜ 0.01).The levels of HYP in lung tissue at different intervals in C group were increasing with time after exposure to PQ,and reached a peak at 28 day,which were significantly lower than those in group B (P ＜ 0.01).The levels of TGF-β1 from different intervals in B group were increased greatly with wider distribution over large portion of lung structure than those in group A,and reached a peak at 7 days,then declined with time,which were significantly higher than those in group A (P ＜ 0.05).The levels of TGF-β1 at different intervals in group C were significantly lower than those in group B (P ＜ 0.05).The levels of HGF at different intervals in B group increased with time,but there was no significant difference among those at different intervals (P ＞0.05).The levels of HGF at different intervals in group B were little bit higher than those in group A,but there was no significant difference between them (P ＞ 0.05).The levels of HGF at different intervals in group C increased with time with significant differences among different intervals (P ＜ 0.05).The levels of HGF at 3 intervals in group C were significantly different from those of group A and group B group (P ＜0.05).Conclusions BMSCs can alleviate pulmonary fibrosis induced by PQ,and increase the survival rate,which may be attributed to decreasing the level of TGF-β1 and increasing the level of HGF.
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Objective: Numerous studies have shown that bone marrow-derived mesenchymal stem cells (MSCs) enhance neurological recovery after cerebral ischemia. However, the mechanisms are still not clear. The present study aimed to investigate the beneficial effects of MSCs on global cerebral ischemia induced by cardiac arrest (CA) and the underlying mechanisms. Methods: Rats subjected to asphyxial CA were injected intravenously with MSCs (5×106 ) at 2 hours after resuscitation. Whole brain histopathologic damage scores (HDS) were assessed by histopathology at 3 and 7 days after resuscitation. The distribution of donor MSCs in the brain was evaluated. The expression of tumor necrosis factor-α-induced protein 6 (TSG-6) and pro-inflammatory cytokines in cerebral cortex was assayed. After intravenous infusion of TSG-6 siRNA-MSCs, HDS and pro-inflammatory cytokines were reevaluated at 7 days after resuscitation. Results: Intravenously administered MSCs significantly reduced whole brain HDS after global cerebral ischemia. Immunofluorescence microscopy revealed that donor MSCs were primarily found in cerebral cortex and expressed TSG-6. MSCs treatment significantly increased the expression of TSG-6 and reduced the expression of pro-inflammatory cytokines in cerebral cortex. In addition, intravenous infusion of TSG-6 siRNA-MSCs failed to attenuate brain inflammation. Conclusion: Systemically administered MSCs reduced inflammatory damage to brain in rats with global cerebral ischemia via secretion of TSG-6.
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Heart Arrest , Mesenchymal Stem CellsABSTRACT
Objective To investigate the protective role of carbon monoxide releasing molecule-2 (CORM-2) in post-resuscitation myocardial dysfunction (PRMD) in rat models of cardiopulmonary resuscitation (CPR).Methods Cardiopulmonary resuscitation model was established after cardiac arrest induced by ventricular fibrillation.Male healthy Sprague-Dawley (SD) rats were randomly (random number) divided into 4 groups according to random number table:control group,CORM-2 group,inactive CORM-2 (iCORM-2) group and Sham group,in which the equal volume (1 mL) of 0.2％ DMSO,50 μmol/kg CORM-2,50 μmol/kg iCORM-2 and 0.2％ DMSO were respectively administered into the rats of these groups after resuscitation.The ejection fraction (EF) of left ventricle and myocardial performance index (MPI) were measured to detect the myocardial function by echocardiography at 12 hours after resuscitation.Mitochondrial respiration was assessed with Clark oxygen electrode at the same time.Western blot was used to determine the ratio of mitochondrial cytochrome c (cyt c) to cytoplasmic cyt c as well as caspase-3 level.Multiple comparisons were made by analysis of variance.Results Compared with the control group,higher EF and MPI,higher state Ⅲ respiration rate and respiratory control rate (RCR) of mitochondria,and decreased ratio of mitochondrial cytc/cytoplasmic cyt c and lower caspase-3 level were observed in the CORM-2 group (P ＜ 0.05).However,there were no significant differences in above biomarkers found between iCORM-2 group and control group (P ＞ 0.05).Conclusions The CO released from CORM-2 might improve mitochondrial respiration and PRMD by inhibition of myocardial apoptosis via a mitochondrial pathway.
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Objective To study the changes in the level of serum IMA in patients with cardiac arrest followed by CPR,and explore the value of serum IMA in predicting prognosis of these patients after CPR.Methods (1) A total of 36 patients (25 men and 11 women) after CPR following cardiac arrest were recruited into experimental group (group C).Of them,15 cases (11 men and 4 women) and 21 cases (14men and 7 women) were assigned into resuscitation group (group R) and non resuscitation group (group NR),respectively,according to the presence or absence of ROSC.Meanwhile,another 60 healthy subjects (39 men and 21 women) matched for age and gender were recruited into healthy control group (group H).(2) The determination of the serum IMA level and comparisons of changes in serum IMA levels among groups were carried out.Results (1) The level of serum IMA in group C was higher than that in group H (P ＜ 0.05) ; The serum IMA level in group R was lower than that in group NR and higher than that in group H (P ＜0.05 for both).(2) The area under the ROC curve for serum IMA in predicting the prognosis of patients treated with CPR after cardiac arrest was 0.73.When the cut off value was 128.25 U/mL,the sensitivity and specificity were 57.1％ and 93.3％ respectively; the positive predictive value and negative predictive value were 92.3％ and 60.9％ ; positive likelihood ratio and negative likelihood ratio were 8.5 and 0.5 ; the correct diagnosis index was 72.2％,and Youden index was 50.5％.Conclusions Serum IMA has a certain value in prediction of prognosis in patients treated with CPR following cardiac arrest.
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Objective To investigate the effects of bone marrow mesenchymal stem cells (MSCs)treatment on TSG-6 in a rat model of cardiopulmonary resuscitation (CPR).Methods Sprague Dawley (SD) rats were randomly (random number) divided into sham group,phosphate buffer solution (PBS)-treated group and MSCs-treated group.Animals were subjected to asphyxial cardiac arrest followed by CPR.In PBS-treated group or MSCs-treated group,animals were injected intravenously with PBS or MSCs at 2h after resuscitation.Neurological deficit scores (NDS) were assessed at 1,3 and 7 d after CPR.Serum S-100B was assayed using enzyme linked immunosorbent assay (ELISA).Immunofluorescence was performed to detect donor MSCs and the expression of TSG-6 in brain.TSG-6 and proinflammatory cytokines in brain were assayed using real time reverse transcription-polymerase chain reaction (RT-PCR).Western blot analysis was performed to measure the levels of neutrophil elastase (NE) in brain.Multiple comparisons were made by analysis of variance.Results At 3d and 7d,MSCs-treated group demonstrated higher NDS than PBS-treated group (P ＜ 0.01),and serum S-100B levels significantly reduced in MSCs-treated group compared with PBS-treated group (P ＜ 0.01).DAPI-labeled MSCs migrated into the ischemic brain and some DAPI + cells colocalized with TSG-6.Compared with PBS-treated group,MSCs treatment significantly up-regulated the expression of TSG-6 and reduced the expression of NE and proinflammatory cytokines in brain at 3 d and 7 d after CPR (P ＜ 0.05).Conclusion Systemically administered MSCs suppressed inflammatory responses in brain after CPR and improved neurological function in rats possibly via induction of TSG-6.
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Objective To study the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from cardiac arrest using a meta-analysis.Methods We searched the MEDLINE (1966-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 (1) the study design was a randomized controlled trial (RCT); (2) the study population included patients successfully resuscitated from cardiac arrest,and received either conventional post-resuscitation care with normothermia or mild hypothermia; (3) the study provided data about good neurologic outcome and survival till hospital discharge.Relative risk (RR) and 95％ corfidence interval (CI) were used to pool the effect.Results The study included four RCTs with a collected total of 417 patients successfully resuscitated from cardiac arrest.Compared to conventional 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 till hospital discharge (RR =1.32,95％ CI 1.08 ～ 1.63,P =0.008).From all over the studies there was no significant difference in reported adverse events between the normothermia and hypothermia group (P ＞ 0.05).There did not exist heterogeneity and publication bias.Conclusions Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from cardiac arrest.
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Objective To investigate the effect of mild therapeutic hypothermia for different lengths of time on cerebral edema and hypoxia-inducible factor 1 α (HIF-1α),vascular endothelial growth factor (VEGF) expressions following intracerebral hemorrhage (ICH) so as to explore possible mechanism for better application of mild hypothermia.Methods ICH models were made in rats by stereotaxically injecting autologous artery blood into right caudate nucleus.Forty male Sprague-Dawley (SD) rats were randomly (random number) divided into 5 groups (n =8 each):sham-operated (sham),normothermic (NT),hypothermic-1 hour (MH1),hypothermic-2 hours (MH2),hypothermic-4 hours (MH3).Normothermic and sham-operated animals were kept at (37.0-± 0.2) ℃ of body temperature.Animals in the hypothermic groups received immediately and rapid cooling after ICH and kept at (33.0 ± 0.5) ℃ of body temperature for 1,2 and 4 hours respectively.Rats were sacrificed at 48 hours after cerebral hemorrhage.Then brain water content and BBB permeability were determined.Quantitative real-time PCR and Western blot were used to analyze the expression of HIF-1α and VEGF.Results The content of brain water,Evans blue concentration in brain,and the mRNA expression and protein levels of HIF-1α and VEGF were noticeably higher in NT group than those in sham group (P ＜0.01).There were statistically significant difference in the expression of HIF-lα mRNA and protein but little difference in other indicators between MH1 group and NT group.Compared with NT group,MH2 group and MH3 group brought about an improvement in BBB permeability and remarkable down-regulation of protein levels and expression of HIF-1 α and VEGF mRNA,whereas there were no statistically significant difference in expression of indicators between the two groups.Conclusions Mild therapeutic hypothermia induced rapidly and immediately after ICH could limit the development of brain edema in rats by down-regulating expression and protein levels of HIF-1 α mRNA,and in turn suppressing the evaluation of VEGF mRNA and protein expression.The brain edema was effectively reduced in animals treated with hypothermia for 2 hours' or 4 hours ' duration with little difference in magnitude of reduction in brain edema between these two modalities of hypothermia.
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Objective: Asphyxia and ventricular fibrillation are the two most prevalent causes of cardiac arrest. The study investigated the differences in brain damage after cardiac arrest between asphyxial and ventricular fibrillation cardiac arrests in rats. Methods: Male healthy Sprague-Dawley rats were randomly assigned to the asphyxial group (cardiac arrest of 6 min, n=15), ventricular fibrillation group (cardiac arrest of 6 min, n=15) and sham group (n=5). Neurologic deficit scores and tape removal test were evaluated at 1, 3 and 7 days after cardiopulmonary resuscitation from three groups. Serum S-100B and brain histopathologic damage scores were also examined. Results: There were no differences in neurologic performance at 1, 3 and 7 days after cardiopulmonary resuscitation between the asphyxial group and ventricular fibrillation group (P>0.05, respectively). Serum S-100B level was higher in the asphyxial group at 1, 3 and 7 days, compared with the ventricular fibrillation group (P<0.05, respectively). There were significantly higher histopathologic damage scores at 1, 3 and 7 days in the asphyxial group compared with the ventricular fibrillation group (P<0.05, respectively). Conclusion: Asphyxial cardiac arrest has worse morphologic brain damage compared with ventricular fibrillation cardiac arrest, but the functional brain damage caused by asphyxial cardiac arrest is similar to that caused by ventricular fibrillation cardiac arrest.
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Objective To explore the incidence,features and outcomes of in-hospital sudden cardiac death (SCD) in order to determine the predictors of survival. Methods The clinical data of 69 patients with cardiac arrest hospitalized from January 2008 through December 2010 were retrospectively analyzed.Information on genders,age,types of arrhythmia was collected and further analyzed to determine these factors associated with the occurrence and outcomes of in-hospital cardiac arrest. Results The overall incidence of SCD was 47.3 / 100 000 per year and 17.4％ of them.survived at discharge.The occurrence rate was higher in male than that in female (66.7％ vs.33.3％,P ＜0.01 ),whereas difference in gender did not affect the discharge rate ( P ＞ 0.05 ). Survivors from in-hospital cardiac arrest were significantly younger than non-survivors (man:62.57 ± 12.83 years vs.75.56 ± 10.55 years; women:60.36 ± 13.24years vs.69.53 ± 11.72 years,P ＜ O.01 ).From 62 ECG records of SCD patients,the incidence of nonshockable rhythms was higher than that of shockable rhythms.Compare to the non-shockable rhythms,the shockable rhythms brought a higher rate of restoration of spontaneous circulation (ROSC) (54.5％ vs.24.5％,P ＜0.05),whereas survival rates at discharge between two groups were not statistically different ( 18.2％ vs.18.4％,P ＞ 0.05 ).Conclusions Non-shockable rhythms were more common in patients suffering from in-hospital cardiac arrest.Although defibrillation treatment contributed benefit to ROSC among patients with ventricular fibrillation or pulseless ventricular tachycardia,high-quality CPR and post-cardiac arrest care may play a more critical role in the outcomes of in-hospital sudden cardiac death.
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Objective To study the characteristics of epidemiology among the emergency patients with acute drugs poisoning in emergency center of Fujian Province.Methods Retrospective study was used to collect data of patients with acute drugs poisoning from 2004 to 2009,and data of patients 'gender,age,cause of poisoning,poison type,emergency diagnosis,medical treatment,etc.were analyzed.Results The epidemiological reports of 744 cases of acute drugs poisoning patients were collcected from 2004 to 2009,the male-to-female ratio was 1:4.2,the average age was 33.0,high incidence group was at ages 18 ～29 (50.3％ ).The most visiting time was in Spring (April to June).Eighty-eight point three percentage of poisoning was intentional.Central nervous system drugs,in particular sedative/hypnotic drugs (64.5％ )was the most common agents associated with poisoning.The poisoned patients were divided into three groups with mild ( 51.5％ ),moderate ( 33.2％ ) and severe ( 15.3％ ) according to the patient' s condition.Thirty-seven percentage poisoned patients were discharged after treatment followed up for observation,and 28.3％ patients were hospitalized,no patients died.Conclusions The majority of acute drugs poisoning among patients from city were sedative/hypnotic drugs.Reasonable grading and different treatment according to the condition of acute drugs poisoning would be helpful to improve the survival rates of acute poisoning and reduce medical costs.
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Objective Acute poisoning is frequently encountered at emergency department. This study was to investigate the epidemiology and characteristics of patients with acute poisoning who were treated at the Emergency Center, Fujian Provincial Hospital, China. Method We retrospectively analyzed the gender, age, causes of poisoning, types of poisons, poisoning route, emergency diagnoses, outcomes, and prognoses of these patients.Results Altogether 2867 patients with acute poisoning were treated from January 2004 to December 2009. The ratween 18 and 40 years old. The incidence of acute poisoning was as high as 11.33% in January each year. The incidence of poisoning was in a descending order: alcohol poisoning (54.55%), medication poisoning (25.95%), pesticide poisoning (5.65%), and drug poisoning (4.88%). Most (56.44%) of the patients with drug poisoning were under 25 years and their mean age was significantly lower than that of patients with medication poisoning or alcohol poisoning ( P ＜ 0.01 ). Approximately 69.54% of the patients were followed up after emergency treatment, 30.39% were hospitalized, and four patients died. Conclusions Acute poisoning is largely alcohol poisoning and medication poisoning in a city. The emergency green channel "pre-hospital emergency care-emergency department-hospital treatment" can significantly improve the survival rate of patients with acute poisoning.
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Objective To investigate the distribution of alpha2-HS glycoprotein (AHSG) gene polymorphisms and the relationships of AHSG gene polymorphisms with atherosclerosis as well as serum bone related biochemical mark-era. Methods Blood samples of 344 hospitalized female patients, aged 20 ～ 80 years, were sampled for serum bone alkaline phosphatase, cross-linked N-telopeptide of collagen type Ⅰ, cross-linked C-telopeptide of collagen type Ⅰ , osteoprotegrin and leptin were determined by ELISA. Serum TC,TG and calcium content were detected. Poly-morphism of AHSG gene was detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme Sac Ⅰ. BMD (Norland XR-36) of the anteroposterior spine (AP), supine lateral spine (Lat) and femoral neck (FN) were measured. Morphological changes in the aorta and bone of type GG patient were detected by pathological microscopy. IMT were measured by color doppler ultrasound equipment(SEQUOIAS12). Results (1) The genotype frequency of CC, CG, and GG were 59.7%, 25.1% and 15.2% respectively in all elderly female patients. There were significant difference in blood lipids, Ca~(2+) and serum bone relative biochemical markers to different AHSG genotypes. (2)There were significant differences in the BMD of the AP, Lat, FN and IMT and the serum biochemical markers among the CC, CG and GG genotypes. (3)GG-female patients bone tissue pathology section verify the AHSG polymorphism genetic mutation and atherosclerosis, osteoporosis development of the relationship. Conclusion There was close relationship among AHSG polymorphism variation and the incidence of arteriosclerosis and osteoporosis in elderly female.
ABSTRACT
Objective To investigate the distribution of alpha2-HS glycoprotein(AHSG) gene polymorphisms and the relationships of AHSG gene polymorphisms with atherosclerosis as well as serum bone related biochemical markers.Methods Blood samples of 344 hospitalized female patients,aged 20～80 years,were sampled for serum bone alkaline phosphatase,cross-linked N-telopeptide of collagen typeⅠ,cross-linked C-telopeptide of collagen type Ⅰ,osteoprotegrin and leptin were determined by ELISA.Serum TC,TG and calcium content were detected.Polymorphism of AHSG gene was detected by polymerase chain reaction fragment length polymorphisms(PCR-RFLP) of restriction enzyme Sac Ⅰ.BMD(Norland XR-36) of the anteroposterior spine(AP),supine lateral spine(Lat) and femoral neck(FN) were measured.Morphological changes in the aorta and bone of type GG patient were detected by pathological microscopy.IMT were measured by color doppler ultrasound equipment(SEQUOIA512).Results(1) The genotype frequency of CC,CG,and GG were 59.7%,25.1% and 15.2% respectively in all elderly female patients.There were significant difference in blood lipids,Ca2+ and serum bone relative biochemical markers to different AHSG genotypes.(2)There were significant differences in the BMD of the AP,Lat,FN and IMT and the serum biochemical markers among the CC,CG and GG genotypes.(3)GG-female patients bone tissue pathology section verify the AHSG polymorphism genetic mutation and atherosclerosis,osteoporosis development of the relationship.Conclusion There was close relationship among AHSG polymorphism variation and the incidence of arteriosclerosis and osteoporosis in elderly female.