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1.
J Magn Reson Imaging ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545977

RESUMO

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

2.
Front Cell Dev Biol ; 9: 628317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777937

RESUMO

The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.

3.
J Healthc Eng ; 2020: 8865264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204405

RESUMO

Objectives: To effectively evaluate the compliance degree between the electronic medical records of Traditional Chinese Medicine (TCM) hospitals, as well as the information platform, and the related information standards of electronic medical records, a standard compliance testing scheme based on electronic medical records of TCM outpatients is proposed. Methods: This research selected the data of clinical outpatients accumulated in 10 years by the Digital Medicine Institute of Chengdu University of TCM and processed the data through security check and desensitization process. And then 28348 cases of processed electronic medical records of TCM outpatients were inputted into the standard compliance testing platform for assessment. The result was then outputted. Results: There are 924 cases among the 28348 that can be rated as five-star medical records, 84 cases four-star, 132 cases three-star, 12460 cases two-star, 13488 one-star, and 1260 cases zero-star through the integrity and standardization test. Conclusion: By the way of assessing the integrity and standardization of data, the standard compliance test algorithm scheme for electronic medical records of TCM outpatients introduced in this paper can solve the problems such as data unavailability caused by ununified codes and incomplete data in the data-sharing process and provides technical support for the construction of data standardization testing in electronic medical records of TCM outpatients.


Assuntos
Registros Eletrônicos de Saúde , Medicina Tradicional Chinesa , Algoritmos , Hospitais , Humanos , Pacientes Ambulatoriais
4.
Zhen Ci Yan Jiu ; 45(6): 431-7, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32643878

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Baihui "(GV20) and "Shenshu "(BL23) on activation of glial cells, expression of inflammatory factor proteins and aquaporin 4 (AQP4)in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease(AD). METHODS: Twenty C57/BL6 background male APP695/PS1-dE9(APP/PS1) double transgenic mice (model group) and 20 wild type (WT) C57/BL6 mice (blank group) were respectively randomized into control and EA groups. EA (2 Hz/15 Hz, 1-2 mA) was applied to GV20 and bilateral BL23 for 30 min, once daily, 6 days a week for 4 weeks. The recognition memory ability was detected by novel object recognition tests in a behavior test box. The percentage of time spent in close interaction with novel object (C) relative to the total time was used to generate preference index. The contents of hippocampal ß amyloid protein (Aß)1-40 and Aß1-42 were assayed using ELISA, and the expression levels of glial fibrillary acidic protein (GFAP), ionic calcium binding receptor molecule-1 (Iba-1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proteins in the hippocampus measured by Western blot. The activities of hippocampal astrocytes (GFAP-labelled cells), microglia (Iba-1-labelled cells) and the polarity expression of AQP4 (for removing Aß) were measured by immunohistochemistry. RESULTS: The preference index was significantly decreased in the model group relatively to the blank control group (P<0.05) and considerably increased in the model+EA group relatively to the model group (P<0.05), suggesting an improvement of the recognition memory after EA. The contents of Aß1-40 and Aß1-42, immunoactivity of GFAP and Iba-1, expression levels of GFAP, Iba-1, IL-1ß, IL-6 and TNF-α proteins were significantly higher in the model group than in the blank control group (P<0.01,P<0.05), while the AQP4 immunoactivity was notably lower in the model group than in the blank control group (P<0.05). Compared with the model group, the levels of Aß1-40 and Aß1-42, GFAP, Iba-1, IL-1ß, IL-6 and TNF-α proteins, and the percentage of Aß plaque area were significantly decreased in the model+EA group (P<0.01,P<0.05), and the immunoactivity of AQP4 was significantly increased in the mo-del+EA group (P<0.05). No significant changes were found in the above-mentioned indexes in the blank+EA group relevant to the blank control group (P>0.05).. CONCLUSION: EA at GV20 and BL23 can reduce inflammatory reaction and Aß level, suppress activation of astrocytes and microglia, and up-regulate expression of AQP4 in the hippocampus tissue in APP/PS1 transgenic mice, which may contribute to its effect in improving recognition memory ability, suggesting a role of EA intervention in delaying the development of AD via promoting the drainage of Aß by the glymphatic system in the brain.


Assuntos
Doença de Alzheimer , Eletroacupuntura , Precursor de Proteína beta-Amiloide , Animais , Aquaporina 4 , Modelos Animais de Doenças , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1
5.
Chin J Integr Med ; 26(6): 420-427, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32361934

RESUMO

OBJECTIVE: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). METHODS: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. RESULTS: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). CONCLUSIONS: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).


Assuntos
Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Chalcona/análogos & derivados , Quinonas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Chalcona/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
6.
Acta Pharmacol Sin ; 40(6): 762-768, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30487649

RESUMO

Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1I2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1I2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed that SNPs NR1I2 rs13059232 and CYP2C19 alleles (2*/3*) were related to CR. SNP NR1I2 (rs13059232) was identified as an independent risk factor for the long-term clinical outcomes in the clopidogrel cohorts (P < 0.001), but similar results were not observed in a matched aspirin cohort (P > 0.05). Our results suggest that NR1I2 variant (rs13059232) could serve as biomarker for clopidogrel therapy and individualized antiplatelet medications in the treatment of acute IS patients.


Assuntos
Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/genética , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X/genética , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Infarto Encefálico/diagnóstico , Estudos de Coortes , Citocromo P-450 CYP2C19/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/genética , Prognóstico , Fatores de Risco
7.
Acta Pharmacol Sin ; 37(11): 1442-1448, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27641736

RESUMO

AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Receptores de Superfície Celular/genética , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Acidente Vascular Cerebral/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Grupo com Ancestrais do Continente Asiático , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Tromboxano B2/biossíntese , Tromboxano B2/sangue , Falha de Tratamento
8.
Nutrients ; 8(6)2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27338470

RESUMO

The association between elevated body mass index (BMI) and risk of death has been reported in many studies. However, the association between BMI and all-cause mortality for hypertensive Chinese adults remains unclear. We conducted a post-hoc analysis using data from the China Stroke Primary Prevention Trial (CSPPT). Cox regression analysis was performed to determine the significance of the association of BMI with all-cause mortality. During a mean follow-up duration of 4.5 years, 622 deaths (3.0%) occurred among the 20,694 participants aged 45-75 years. A reversed J-shaped relationship was observed between BMI and all-cause mortality. The hazard ratios (HRs) for underweight (<18.5 kg/m²), overweight (24.0-27.9 kg/m²), and obesity (≥28.0 kg/m²) were calculated relative to normal weight (18.5-23.9 kg/m²). The summary HRs were 1.56 (95% CI, 1.11-2.18) for underweight, 0.78 (95% CI 0.64-0.95) for overweight and 0.64 (95% CI, 0.48-0.85) for obesity. In sex-age-specific analyses, participants over 60 years of age had optimal BMI in the obesity classification and the results were consistent in both males and females. Relative to normal weight, underweight was associated with significantly higher mortality. Excessive weight was not associated with increased risk of mortality. Chinese hypertensive adults had the lowest mortality in grade 1 obesity.


Assuntos
Índice de Massa Corporal , Hipertensão/mortalidade , Mortalidade , Idoso , Grupo com Ancestrais do Continente Asiático , Glicemia/metabolismo , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Jejum , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/mortalidade , Modelos de Riscos Proporcionais , Fatores de Risco , Triglicerídeos/sangue
9.
Acta Pharmacol Sin ; 37(7): 882-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27133299

RESUMO

AIM: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. METHODS: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped. RESULTS: The CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). CONCLUSION: The individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.


Assuntos
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Resistência a Medicamentos/genética , Receptores Purinérgicos P2Y12/genética , Receptores de Esteroides/genética , Ticlopidina/análogos & derivados , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Clopidogrel , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão/genética , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico
10.
Dement Geriatr Cogn Dis Extra ; 1(1): 276-82, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22545038

RESUMO

BACKGROUND: Subcortical ischemic vascular dementia (SIVD) has been proposed as the most frequent subtype of vascular cognitive impairment. The aim of this study was to evaluate the psychometric properties of the Chinese (Cantonese) Montreal Cognitive Assessment (CC-MoCA) in patients with SIVD in the Guangdong Province of China. METHODS: 71 SIVD patients and 60 matched controls were recruited for the CC-MoCA, Mini Mental State Examination and executive clock drawing tasks. Receiver-operating characteristic curve analyses were performed to determine optimal sensitivity and specificity of the CC-MoCA total score in differentiating mild vascular dementia (VaD) patients from moderate VaD patients and controls. RESULTS: The mean CC-MoCA scores of the controls, and mild and moderate VaD patients were 25.2 ± 3.8, 16.4 ± 3.7, and 10.0 ± 5.1, respectively. In our study, the optimal cutoff value for the CC-MoCA to be able to differentiate patients with mild VaD from controls is 21/22, and 13/14 to differentiate mild VaD from moderate VaD. CONCLUSION: The CC-MoCA is a useful cognitive screening instrument in SIVD patients.

11.
Can J Physiol Pharmacol ; 88(9): 907-17, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20921977

RESUMO

This study aimed to investigate the protective effect of Apocynum venetum leaf extract (AVLE) on an in vitro model of ischemia-reperfusion induced by oxygen and glucose deprivation (OGD) and further explored the possible mechanisms underlying protection. Cell injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage; cell viability was measured by XTT reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8, and -9 activation and Bcl-2/Bax protein expression were determined by Western blot analysis. We report that treatment with AVLE (5 and 50 µg/mL) effectively reduced neuronal cell death and relieved cell injury induced by OGD. Moreover, AVLE decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspase-3 and -8 and Bax, and inhibited the reduction of Bcl-2 expression. These findings indicate that AVLE protects against OGD-induced injury by inhibiting apoptosis in rat cortical neurons by down-regulating caspase-3 activation and modulating the Bcl-2/Bax ratio.


Assuntos
Apocynum/química , Córtex Cerebral/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/patologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/metabolismo , Microscopia Eletrônica de Transmissão , Neurônios/metabolismo , Neurônios/ultraestrutura , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Acidente Vascular Cerebral/tratamento farmacológico
12.
J Ethnopharmacol ; 131(1): 154-64, 2010 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-20600765

RESUMO

AIM OF THE STUDY: To investigate the neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides (GLPS) on cerebral ischemic injury in rats, and to explore the involved mechanisms. MATERIALS AND METHODS: Two models [middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats and oxygen and glucose deprivation (OGD) in primary cultured rat cortical neurons] were employed to mimic ischemia-reperfusion (I/R) damage, in vivo and in vitro, respectively. Cerebral infarct area was measured by tetrazolium staining, and neurological functional deficits were assessed at 24h after I/R. Neuronal apoptosis was studied by Nissl staining and DNA fragmentation assay. Neuronal injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage, cell viability was measured by sodium 3'-1- (phenylaminocarbonyl)-3, 4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid (XTT) reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8 and -9 activation and Bcl-2, Bax protein expression were determined by western blot analysis. RESULTS: Oral administration of GLPS (100, 200 and 400mg/kg) significantly reduced cerebral infarct area, attenuated neurological functional deficits, and reduced neuronal apoptosis in ischemic cortex. In OGD model, GLSP (0.1, 1 and 10 microg/ml) effectively reduced neuronal cell death and relieved cell injury. Moreover, GLPS decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspases-3, -8 and -9 and Bax, and inhibited the reduction of Bcl-2 expression. CONCLUSIONS: Our findings indicate that GLPS protects against cerebral ischemic injury by inhibiting apoptosis by downregulating caspase-3 activation and modulating the Bcl-2/Bax ratio.


Assuntos
Isquemia Encefálica/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Reishi , Água , Animais , Isquemia Encefálica/patologia , Células Cultivadas , Frutas , Masculino , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Solubilidade
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