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Objective:To explore the effect of rapamycin on 1-methyl-4-phenylpyridinium iodide (MPP+ )-induced activation of Nod-like receptor protein 3 (NLRP3) inflammasome in microglia.Methods:The BV2 microglia cells were divided into control group, model group and rapamycin group.The model group and rapamycin group were treated by MPP+ to activate NLRP3 inflammasome, and rapamycin group was pretreated with rapamycin.Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA levels of NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1.Immunofluorescence was used to detect the protein expression of NLRP3 and interleukin-1β (IL-1β). Western blot was carried out to assess the protein expression of NLRP3, ASC, caspase-1, beclin1 and microtubule-associated protein 1 light chain 3 (LC3).Results:The mRNA levels of NLRP3, ASC and caspase-1 in model group were higher than those in control group ( t=4.825, 3.015, 5.853, all P<0.05). The mRNA levels of NLRP3 and caspase-1 in rapamycin group were lower than those in model group ( t=2.75, 2.89, both P<0.05). In model group, the protein expressions of NLRP3 (1.54±0.22), ASC (1.02±0.13) and caspase-1 (1.42±0.30) were higher than NLRP3 (0.66±0.15), ASC (0.41±0.14) and caspase-1 (0.70±0.10) in control group ( t=5.653, 5.602, 3.964, all P<0.01), while the protein expression of beclin1 (0.28±0.09) and LC3II/LC3I ratio(0.69±0.14) were lower than beclin1 (0.60±0.11) and LC3II/LC3I (1.29±0.23) in control group ( t=4.010, 3.982, both P<0.01). The protein expressions of NLRP3 (0.80±0.18) and ASC (0.68±0.14) in rapamycin group were lower than those in model group ( t=4.413, 3.077, both P<0.05), while the protein expression of beclin1 (0.65±0.20) and LC3II/LC3I ratio(1.42±0.36) were higher than those in model group ( t=2.965, 3.278, both P<0.05). Conclusion:MPP+ activates NLRP3 inflammasome and impairs autophagic function in microglia.Rapamycin inhibits MPP+ -induced activation of NLRP3 inflammasome by restoring autophagic impairment in microglia.
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Objective To investigate the effects and regulating mechanisms of matrix metalloproteinase 9 (MMP-9) gene silencing on aquaporin 4(AQP4) expression in astrocytes induced by oxygen-glucose deprivation.Methods Cerebral cortical astrocytes from 2 days newborn SD rats were undergone the primary culture.The ischemic cell model was established by oxygen-glucose deprivation.This experiment were divided into control group,negative control group and MMP-9 gene silencing group.The leakage rate of lactated dehydrogenase (LDH)was detected by chromatoptometry.The MMP-9 gene silencing was carried out by Lentivirus transfection.Real-time fluorescence quantitative PCR and Western blot were used to detect the expression levels of AQP4 and MMP-9.The expressions of PKA,PKC,PKG and CaMK Ⅱ were determined by Western blot.Results Compared with control group,LDH leakage rate was significantly higher in astrocytes induced by oxygen-glucose deprivation(t=13.35,P＜0.01).The expression of MMP-9 mRNA in astrocytes in MMP-9 gene silencing group(0.412±0.297) decreased significantly compared with that in negative control group(1.118 ± 0.240) (t =-4.964,P＜ 0.05).The expression of AQP4 mRNA in astrocytes in MMP-9 gene silencing group(1.002±0.082) decreased significantly compared with that in negative control group(1.442±0.066) (t=-9.886,P＜0.01).The expression of AQP4 protein in astrocytes in MMP-9 gene silencing group(0.643±0.036)decreased significantly compared with that in negative control group(1.000± 0.069)(t=-11.073,P＜0.01).The expression of PKC protein in astrocytes in MMP-9 gene silencing group (0.198±0.110)decreased significantly compared with that in negative control group (0.980± 0.232) (t =-7.218,P＜0.01).The expressions of PKA(t=0.875),PKG(t=0.818) and CaMK Ⅱ (t=0.933) protein had no statistically significant difference between negative control group and MMP-9 gene silencing group(all P＞0.05).Conclusion The permeability of astrocytes is increased by oxygen-glucose deprivation.Gene silencing MMP-9 could induce expression of AQP4 mRNA and protein decreased,and MMP-9 may regulate AQP4 expression by regulating PKC activity.
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Objective To investigate the perioperative complications of stenting with symptomatic intracra-nial artery stenosis and study the mechanism and prevention of complications. Methods 63 patients were collect-ed from Stroke Center of Guangxi. They were proved intracranial artery stenosis and performed intracranial stents. Patients′ age,with hypertension,diabetes and hyperlipidemia or not,smoking or not,types and occurrence time of complications were registered. Results 63 patients were registered and 2 patients terminated operation due to blood vessels circuity or serious vessel spasm. Operation success rate reached 96.83％. 5 patients had complications among 63 cases,with complication incidence of 8.20％. 3 patients experienced cerebral hemorrhage and two cere-bral infarction in peri-operation period. 2 patients died of complications and mortality rate was 3.28％. Conclu-sions The incidence rate of complications of intracranial stenting with symptomatic intracranial artery stenosis is relatively high and it can be reduced by preoperative sufficient assessment and prudent selection ,careful operation and strict management after operation.
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Objective To explore the risk factors of poststroke infection after cerebral infarction. Methods We consecutively included 283 patients with acute ischemic infarcts confirmed by diffusion-weighted imaging (DWI) within 72 hours from Guangxi stroke center. Based on infection status, patients were divided into Not infection group(n=198) and infection group (n=85). The serum cortisol and plasma IL-4 were assessed using chemiluminescent system and double antibody sandwich enzyme linked immunosorbent assay at admission and seventh day later,respectively. Results Compare to no infection group, smoking, mechanical ventilation, diabetes mellitus, dysphagia, COPD,level of consciousness, cortisol and IL-4 at admission, NIHSS, middle area and large area infarction, large atherosclerosis and cardiogenic infarction, left side,both side and subtentorial infarction are more liable to infection(P<0.05);After a Single-factor and Multivariate analysis,we found that cortisol(OR 3.26)and IL-4(OR 2.83)at admission,large area infarction(OR 2.67),left side(OR 3.78)and subtentorial infarction(OR 3.12)were significant correlated with infection, suggesting that they might be the independent risk factors for infection after cerebral infarction. Conclusion Immunological factors and different regional cerebral infarction may increase susceptibility to infection after stroke.
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Objective To investigate the perioperative complications of stenting with symptomatic intracra-nial artery stenosis and study the mechanism and prevention of complications. Methods 63 patients were collect-ed from Stroke Center of Guangxi. They were proved intracranial artery stenosis and performed intracranial stents. Patients′ age,with hypertension,diabetes and hyperlipidemia or not,smoking or not,types and occurrence time of complications were registered. Results 63 patients were registered and 2 patients terminated operation due to blood vessels circuity or serious vessel spasm. Operation success rate reached 96.83％. 5 patients had complications among 63 cases,with complication incidence of 8.20％. 3 patients experienced cerebral hemorrhage and two cere-bral infarction in peri-operation period. 2 patients died of complications and mortality rate was 3.28％. Conclu-sions The incidence rate of complications of intracranial stenting with symptomatic intracranial artery stenosis is relatively high and it can be reduced by preoperative sufficient assessment and prudent selection ,careful operation and strict management after operation.
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Objective To analyze lesion patterns of lacunae-sized infarctions in the perforating arterial territory in terms of shape and determine whether the lesion patterns associate with their prognosis. Methods We consecutively included patients with confirmed lacunae-sized acute ischemic infarcts in the penetrating arterial territories on diffu?sion-weighted imaging(DWI)from Guangxi stroke center between June 2012 to September 2013. Based on diffu?sion-weighted MRI, the shape of ischemic infarcts were divided into oval or conglomerated beads shape. Demographics, risk factors and NIH Stroke Scale (NIHSS) score at admission and discharge, Ranking score after three months and stroke mechanisms were analyzed. Results Among 189 patients, the conglomerated beads shape and oval shape of infarcts were detected in 69(36.5%)and 120(63.5%)patients, respectively. There were not difference between these two groups in de?mographics, risk factors and NIH Stroke Scale (NIHSS) score at admission. However, the maximal diameter of the lesion was significantly larger in the conglomerated beads shape group than in the oval shape (13.8±2.3 mm vs. 10.6±3.2 mm, P=0.006). Early neurologic deterioration was also more commonly detected in the conglomerated beads shape group than in the oval shape group (24.6% vs. 5.0%,P=0.009). Early neurologic rehabilitation was slower in the conglomerated beads shape group than in the oval shape group(30.5% vs. 10.8%,P=0.018). Multiple logistic regression analysis showed that the conglomerated beads shape was significantly associated with early neurologic deterioration (OR=7.55, 95%CI:1.73~33.25,P=0.010) and was negatively related to early neurologic rehabilitation(OR=5.75, 95%CI:1.53~28.70,P=0.030). Conclusions The conglomerated beads shape of lacunae infarction is significantly associated with ear?ly neurologic deterioration and is negatively related to early neurologic rehabilitation.