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ObjectiveTo observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout （ApoE-/-） mice， and explore its mechanism of treating atherosclerosis by regulating intestinal flora. MethodThirty-two 8-week-old male ApoE-/- mice were randomly divided into model group， rosuvastatin group （10 mg·kg-1）， high-， low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis （75， 25 mg·kg-1）， with 8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration， blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin （HE） staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16S rRNA amplicon sequencing was used to detect intestinal flora. ResultCompared with the blank group， the plaque area of the model group was significantly increased with inflammatory infiltration， the contents of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， inflammatory factors and inducible nitric oxide synthase （iNOS） were increased， while the content of high-density lipoprotein cholesterol （HDL-C） was decreased. Compared with the model group， rosuvastatin group and high- and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque， reduce the contents of TG， TC， LDL-C， inflammatory factors and iNOS， and increase the content of HDL-C. Compared with the blank group， the relative abundances of Firmicutes and Proteobacteria in the model group increased， while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated， and the total number and abundance of intestinal flora species in the model group were low. Compared with the model group， ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria. ConclusionEthyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids， which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE-/- mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors， improve antioxidant capacity and repair the disorder of intestinal flora structure.
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Diffuse axonal injury (DAI) is a common primary brain injury.The main mechanism of DAI is the relative displacement of brain tissue junction caused by shearing force during cranial rotation.The pathological changes are the deformation and rupture of white matter nerve fiber bundles.The mechanism of injury and recovery is still unclear,and unified diagnostic criteria are also lacking.Apolipoprotein E (APOE) gene polymorphisms are associated with nervous system development,injury,and repair process.The APOE gene contains six genotypes by the combination among three genes and synthesizes three proteins including apoE2,apoE3 and apoE4.The abnormal spatial structure of apoE4 decreases its ability of transporting lipids,resulting in reduced repair ability after nerve injury.The molecular mechanism of ApoE in the development of axonal injury is complicated.apoE protein can bind to receptor proteins such as low density lipoprotein receptor related protein 1 (LRP1) and heparan sulfate proteoglycan (HSPG) to mediate axonal repair,and it can also damage nerves by influencing calcium influx and producing toxic fragments through hydrolysis.Correcting the abnormal structure of apoE4 is helpful to nerve repair,and apoE analogues also have certain neuroprotective effects.This article reviews the injury characteristics,pathological characteristics,APOE gene polymorphisms,and the role of apoE synthesis in DAI,to provide new insights for elucidation of mechanism of DAI and related clinical application.
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OBJECTIVE: To establish a PC12 cell line with stable expression of human apolipoprotein E( ApoE4) gene by transfection with a lentiviral vector carrying human ApoE4 gene and to investigate the effect of maltol aluminum on the viability of transfected PC12 cells. METHODS: The lentiviral vector carrying human ApoE4 gene was transfected into PC12 cells. PC12 cells with overexpression of ApoE4 gene and negative control vector were obtained after puromycin screening.The mRNA relative expression of R-Apo E and( or) H-Apo E-FLAG of cells in PC12,PC12-NC and PC12-ApoE4 groups were detected by real-time fluorescent quantitative polymerase chain reaction,and the effect of cell construction was identified. PC12-ApoE4 cells and PC12 cells were exposed to maltol aluminum solution at concentrations of 0. 00,100. 00,200. 00 and 400. 00 μmol/L respectively for 24 hours,and cell viability was detected by Cell Counting Kit-8( CCK-8)assay. RESULTS: PC12-ApoE4 and PC12-NC cells under the fluorescence microscope showed fluorescence expression,suggesting that transfection was successful. The expression of PC12 cells showed no fluorescence. The relative expression of H-Apo E-FLAG gene mRNA( the median amount) of PC12-ApoE4 cells was 148. 74,which was higher than the R-Apo E gene in PC12 cells( 1. 00) and PC12-NC cells( 1. 01)( P < 0. 01). After exposure to maltol aluminum,the cell survival rates in terms of the main effect and interaction effect of dose and cell type were statistically significant( P < 0. 01),among them,the cell viabilities were decreased in the concentration range of 0. 00-400. 00 μmol/L with the dose of maltol aluminum exposure increased,showing dose-effect relationship( P < 0. 01). CONCLUSION: The cell line stably expressed human ApoE4 gene was constructed successfully. There was interaction between the effects of maltol aluminum and ApoE4 gene on the survival rate of PC12 cells,and ApoE4 gene could enhance the cytotoxicity of maltol aluminum on PC12 cells.
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Objective:To study the Xinjiang Kazakh,Han nationality patients with coronary heart disease apolipoprotein E gene promoter region rs405509 (G-T),rs449647 (A-T),rs7259620 (G-A) whether there exist differences in the two national distribution between loci polymorphism.Methods:201 cases were studied.DNA product was extracted by using the PheNol-chloroform method and the PCR outcome was purified.We take advantage of multiple single base extension reaction to make DNA Sequencing on The ABI3130XL.Results: The Kazak and Han patients in Xinjiang area in the apolipoprotein E gene promoter rs449647 ( A-T) was statistically significant differences in genotype and allele in two ethnic groups (P0.05).Conclusion:Apolipoprotein E promoter rs449647 ( A-T ) genotype and allele polymorphism have significant differences between Han nationality and Kazak nationality in Xinjiang,others have no statistic difference between the two ethnic groups.
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Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD). Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE) were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM), 42.2% methionine valine (MV), 12.1% valine (VV); and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05). There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.
Polimorfismo do códon 129 do gene da proteína priônica não é fator de risco para doença de Alzheimer A interação entre proteína priônica e oligômeros b-amiloide foi demonstrada recentemente. Homozigose no códon 129 do gene da proteína priônica (PRNP) é fator de risco para doença de Creutzfeldt-Jakob. Este polimorfismo foi estudado como possível fator de risco para doença de Alzheimer (DA). Objetivo Estudar uma possível associação entre o polimorfismo do códon 129 e DA. Métodos Foram investigados 99 pacientes com DA e 111 controles em relação ao polimorfismo do códon 129 e sua associação com desempenho cognitivo. Foram pesquisados outros polimorfismos do PRNP e efeito aditivo do gene da apolipoproteína E (ApoE). Resultados Distribuição no códon 129: 45,5% metionina (MM), 42,2% metionina valina (MV), 12,1% valina (VV) nos pacientes com DA; e 39,6% MM, 50,5% MV, 9,9% VV, nos controles (p >0.05). Não houve diferença no desempenho cognitivo em relação ao códon 129. Estratificação pelo genótipo do ApoE não mostrou diferença entre grupos. Conclusão Polimorfismo do códon 129 não é fator de risco para DA em pacientes brasileiros.
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Aged , Aged, 80 and over , Female , Humans , Male , Alzheimer Disease/genetics , Codon/genetics , Polymorphism, Genetic/genetics , Prions/genetics , Age Factors , Apolipoproteins E/genetics , Brazil , Case-Control Studies , Cognition , Gene Frequency , Risk Factors , Sex FactorsABSTRACT
Objective To observe the effect of Ruanmailing Oral Liquid on angiogenesis in atherosclerosis plaque of Apolipoprotein E (ApoE) gene knock-out mice, and explore the mechanisms of plaque stabilizing. Methods Totally 30 mice 6-8 weeks old ApoE knockout mice were fed a high fat diet for 12 weeks until the formation of a mature atherosclerotic plaque. They were randomly divided into three groups-model group, Ruanmailing group, simvastatin group, with another 6 normal C57BL/6J mice as the control group, and were administered for 12 weeks. Blood was extracted from orbital venous to measure the lipid (TC, TG, LDL-C, HDL-C) variation. HE-stain was used to observe aortic pathomorphological changes, meanwhile, immunohistochemical method was adopted to determine the microvessel density of plagues which is marked by CD105, as well as the expression of CD105 in aorta. Results Compared with the model group, TC, LDL-C, TG of Ruanmailing group and simvastatin group decreased significantly, while HDL-C increased significantly (P0.05). Conclusion Ruanmailing Oral Liquid may reduce the expression of CD105 and inhibit the angiogenesis within the plaque, which is the possible mechanism of stabilizing the atherosclerotic plaque.
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Objective To investigate the influence of aerobic exercise on the vulnerability of atherosclerotic plaques and to observe the concentration of matrix metalloproteinase-9 ( MMP-9 ) and matrix metalloproteinase-14(MMP-14) in carotid atherosclerotic plaques in apolipoprotein E (APoE) gene deficient mice.Methods Eighty male, APoE gene deficient mice were divided into two equal groups: an aerobic exercise group and a limited action control group. Carotid atherosclerotic lesions were induced by perivascular constrictive collars placed on the right common carotid artery. Blood lipid levels in the exercise group were measured after 8 weeks of treadmill running and also in the control group. The morphological characteristics of carotid atherosclerotic plaques were observed in the two groups. Plaque area and fibrous cap thickness were measured. Lipid and collagen positive areas were quantified and the ratios correlated with the entimal areas were calculated. Plaque rupture rate and vulnerable index were calculated.Immunostaining was used to detect MMP-9 and MMP-14 expression in the atherosclerotic plaques. The mRNA levels of MMP-9 and MMP-14 mRNA in the fresh carotid plaques were quantified using a real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Western blotting was performed for examining MMP-9 and MMP-14 protein expression in the fresh carotid plaques.Results No significant difference in serum lipid profiles or plaque area was found between the exercise and control groups. Compared with the control group, mean fibrous cap thickness, cap/core ratio and collagen content were all significantly higher in the exercise group, and lipid content was significantly lower. Plaque rupture rate and the vulnerable index were both significantly lower in the exercise group. Immunostaining showed that MMP-9 and MMP-14 expression were lower in the exercise group compared with the control group.The mRNA expression of MMP-9 and MMP-14 was also significantly lower.Conclusions Aerobic exercise can decrease the expression of MMP-9 and MMP-14 in carotid atherosclerotic plaques in ApoE gene deficient mice. Aerobic exercise may play a role in forestalling atherosclerosis by increasing the stability of plaque and decreasing plaque vulnerability.
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Objective To investigate the association between the apolipoprotein E (apoE) gene polymorphism and the dose for warfarin individual maintenance. Methods The genotypes of 249 patients with warfarin treatment in maintenance doses were determined by PCR/DHPLC assay. The doses for warfarin maintenance were compared among patients with different genotypes. Results In the total of 249 patients, the frequencies of 2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4 genotype were 1.20%, 15.66%, 1.80%, 72.29%, 9.24%, 0.80%, respectively; the allele frequencies of ε2, ε3, ε4 were 9.44%, 84.74%, 5.82%, respectively. The warfarin dose of group ε2 (ε2/ε2, ε2/ε3) was (3.24±1.36) mg/d, slightly higher than that of group ε3 (ε3/ε3, 2.91±1.14 mg/d) or group ε4 [ε4/ε4, ε3/ε4, (2.98±1.05) mg/d], but the difference of the warfarin doses among the 3 groups did not reach statistical significance (F=1.848,P＞0.05). Conclusion ApoE polymorphism may be not a major genetic factor that influences the individual dose for warfarin maintenance.
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Objective To further investigate the relationship between apolipoprotein E(APOE) genotype and trait anxiety in patients with coronary heart disease (CHD).Methods Use the state-trait anxiety inventory (STAI) to investigate the state anxiety and trait anxiety of 107 CHD patients.According the score of TAI,the CHD patients were divided into CHD with high trait anxiety group ( n=39)and low trait anxiety group(n=68).The genotypes and alleles of apolipoprotein E gene was detected in all CHD patients and 50 healthy control subjects with the polymerase reaction(PCR) and restriction fragment length polymorphisms(RFLP) technique.Correlation analysis and logistic regression analysis were used.Results Apolipoprotein E gene showed positive relationship with trait anxiety score( OR =9.251,95％ CI2.726 ～ 18.266).F4 allele entered the regression equaltion Y =30.252 + 0.048X3 (P ＜ 0.05 ).Conclusion The results suggest the polymorphisms of Apolipoprotein E e4 allele may be associated with the trait anxiety symptom.
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@#ObjectiveTo explore the Apolipoprotein-E （ApoE） gene polymorphism in patients with Alzheimer's disease （AD）, vascular dementia (VD) or mild cognitive impairment (MCI). MethodsPeripheral blood was taken from patient with AD, VD or MCI to determine the ApoE genotypes. ResultsThe most of the patients were ε3/ε3 genotype, while the ε2/ε2 and ε4/ε4 could not be detected. ε3/ε4 genotype （P=0.001） and ApoE ε4 allele （P=0.013） was more frequent in AD than in MCI. ApoE ε4 was more frequent in VD than in MCI （P=0.044）. ConclusionApoE ε4 allele is a risk factor in AD, and may be associated with VD and MCI.
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Objective To test amyloid beta protein(Aβ)40 and Aβ42 levels in CSF and apolipoprotein E (ApoE) genotype in patients with Alzheimer's disease(AD) and study whether or not the Aβ is related to the severity of dementia and the genotypes of ApoE.Methods 48 AD patients including 27 cases of mild type and 21 cases of serious type and 35 normal controls were selected.Aβ40 and Aβ42 in CSF and ApoE genotype were analyzed.Results Aβ40 levels were ( 12.3 ±4.6) μg/L,( 11.7 ±4.1 ) μg/L,( 12.6 ±4.9) μg/L and ( 11.0 ±3.7) μg/L(t = 1.377,0.705 and 1.385 ,all the p values were greater than 0.05) and Aβ42 levels were ( 105.3 ±25.4) ng/L,(110.7 ±21.7) ng/L,(96.9 ±23.9) ng/L and (123.5 ±29.6) ng/L(t=3.006,2.832,and 3.488,all the p values less than 0.01 ),in AD group,mild AD group,moderate to serious AD group and normal controls,respectively.Aβ40 levels were (11.9 ± 5.2) μg/L vs.(10.5 ± 3.8) μg/L in AD and controls with ApoEε4(t=0.696,P＞0.05) and (12.6 ±4.5) μg/L vs.(11.4 ±3.4) μg/L without ApoEε4(t = 1.008,P＞0.05).Aβ42 levels were (99.7 ± 23.8) ng/L vs.( 129.6 ± 31.0) ng/L in AD and controls with ApoEε4( t =1.632,P ＞ 0.05 ) and ( 110.4 ± 28.4) ng/L vs.( 129.6 ± 31.0) ng/L in those without ApoEε4 ( t = 2.110,P ＜0.05 ).Conclusions The CSF level of Aβ is abnormal in AD,and it is related to the severity of the disease and the ApoE genotypes.
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AIM: To investigate the effect of detoxifying herbs polygonum cuspidatum, and hawthorn, herb of promoting blood flow, on pathologic morphology and inflammatory factors in apolipoprotein E gene knockout mice, in order to approach the possible regulatory mechanism of polygonum cuspidatum and hawthorn for treating artherosclerosis (AS) unstable plaque. METHODS: The animals were divided into 7 groups (12 mice in every group). The ApoE (-/-) mice fed with high fat diet were divided into polygonum cuspidatum group, hawthorn group, polygonum cuspidatum + hawthorn group, Xuezhikang group and high fat diet model group. Moreover, ApoE (-/-) mice fed with normal diet (normal diet group) and C57BL/6J mice fed with normal diet (normal control group) were set up. After intragastric administration for 17 weeks, serum hs-CRP was detected, aorta structure was observed under light microscope and NF-κB protein expression was determined by immunohistochemistry. RESULTS: The pathological change of AS in aorta in all groups fed with high fat diet and normal diet group were observed with different degree. The changes of aortic lesion in all treatment groups were reduced. The levels of NF-κB and hs-CRP in high fat diet group were significant higher than those in normal control group and normal diet group. Serum NF-κB and hs-CRP levels decreased in every treatment group, which were significant different from those in high fat diet model group (P<0.01). Among them, the changes in polygonum cuspidatum and hawthorn groups were the best. CONCLUSION: Chinese herbs of polygonum cuspidatum and hawthorn reduce inflammatory factors NF-κB and hs-CRP expression and play a role in anti-AS formation.
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@#Objective To study the dynamic changes in cardiac morphology and myocardial collagen in apolipoprotein E-deficient (apoE-/-) mice of different age with cholesterol-fed. Methods 18 male apoE-/- mice were randomized into 3 groups: 24 weeks group （n=6）, 32 weeks group （n=6）, 40 weeks group （n=6）. 8 C57BL/6J mice were set as the control. Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, high-density lipoprotein cholesterol (HDL-C) were determined. The cardiac morphological changes and the myocardial collagen were observed. Results Compared with the 24 weeks group, the content of myocardial collagen of 32 and 40 weeks group significantly increased (P<0.05). Conclusion With the increasing of age, TC significantly increased, myocardial collagen content tended to go up.
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BACKGROUND/AIMS: Apolipoprotein E (Apo E) is important in plasma lipid metabolism and is a component of several plasma lipoprotein-lipid particles. Three major Apo E isoforms are encoded by three common allelic forms, epsilon2, epsilon3, and epsilon4 at the APO E locus. The goal of this study was to examine the association between polymorphisms in the apolipoprotein E gene (APOE) and fatty liver disease. METHODS: We examined the distribution of APOE alleles from 116 fatty liver patients and 50 controls in Korea. RESULTS: The frequencies of APOE alleles in fatty liver patients were 6.5% in epsilon2, 85.7% in epsilon3 and 7.8% in epsilon4. The corresponding frequencies in control subjects were 4.0% in epsilon2, 91.0% in epsilon3 and 5.0% in epsilon4. There were no significant differences in the distribution of APOE genotypes between fatty liver patients and controls. APOE epsilon2 and epsilon4 allele frequencies in fatty liver patients were more than those in controls. However, there was no significant differences in APOE epsilon2 and epsilon4 allele frequencies. CONCLUSIONS: These results suggest that APOE alleles seem not to be directly associated with the pathogenesis of fatty liver disease.
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Adult , Aged , Female , Humans , Male , Middle Aged , Apolipoproteins E/genetics , English Abstract , Fatty Liver/genetics , Gene Frequency , Polymorphism, GeneticABSTRACT
0.05).Conclusion In Chinese,ApoE allele ?2 may be a risk factor for developing diabetic nephropathy complication.No correlation between ApoE gene polymorphism and type 2 diabetes mellitus was found in Chinese.