目的 探索α-突触核蛋白(α-Syn)干预对人单核细胞白血病细胞系(THP-1)巨噬细胞源性泡沫细胞的影响。方法 通过佛波酯(PMA)和氧化型低密度脂蛋白(ox-LDL)构建THP-1巨噬细胞源性泡沫细胞模型,使用不同浓度(33、66、100、133 nmol/L)α-Syn处理泡沫细胞,随后检测细胞胆固醇含量和炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)及白细胞介素-8(IL-8)的mRNA表达以及核因子κB(NF-κB)和凝集素样氧化低密度脂蛋白受体-1(LOX-1)的蛋白表达变化。结果 高剂量(100和133 nmol/L)α-Syn处理可以减少THP-1巨噬细胞源性泡沫细胞内胆固醇的含量(P<0.05),并且减少IL-1β、IL-6和IL-8的mRNA表达(P<0.05)。进一步发现(100 nmol/L和133 nmol/L)α-Syn可以降低THP-1巨噬细胞源性泡沫细胞p-NF-κB和LOX-1的蛋白表达(P<0.05)。结论 α-Syn可以降低THP-1源性巨噬细胞泡沫细胞胆固醇蓄积和炎症反应,可能是通过下调p-NF-κB和LOX-1蛋白表达。
Objective To explore the effects of α-synuclein(α-Syn)intervention on human monocytic leukemia cell(THP-1)macrophage-derived foam cells.Methods The THP-1 macrophage-derived foam cell model was constructed by phorbol 12-myristate 13-acetate(PMA)and oxidized low-density lipoprotein(ox-LDL).Foam cells were treated with different concentrations(33, 66, 100, and 133 nmol/L)of α-Syn, and the cellular cholesterol contents, as well as the mRNA expression of IL-1β、IL-6 and IL-8 were detected.Subsequently,alternation in protein expression of NF-κB and LOX-1 was measured.Results High-dose(100 and 133nmol/L)α-Syn treatment significantly reduced the levels of intracellular cholesterol in THP-1-derived macrophage foam cells(P<0.05)and decreased the mRNA expression of IL-1β、IL-6 and IL-8(P<0.05).It was further found that(100 nmol/L and 133 nmol/L)α-Syn decreased the protein expression of p-NF-κB and LOX-1 in THP-1 macrophage-derived foam cells(P<0.05).Conclusions The results of the present study suggest that α-Syn reduces cholesterol accumulation and inflammatory response in THP-1-derived macrophage foam cells, possibly by down-regulating p-NF-κB and LOX-1 protein expression.
目的 探讨载脂蛋白E(ApoE)基因多态性与卒中后认知障碍的相关性,即大动脉粥样硬化型脑梗塞的严重程度。方法 采用病例——对照研究的方法,收集九江学院附属医院神经内科的100例急性缺血性脑卒中且病因分型为大动脉粥样硬化型患者(脑梗死组)和50例性别、年龄匹配的非缺血性脑卒中患者(对照组)。检测患者的 ApoE 基因型、血脂、美国国立卫生院卒中量表(NIHSS)、卒中后6个月简易智力状态检查量表(MMSE)等,采用多因素方差分析等统计学方法分析他们之间的关联性。结果 ApoE 3/4基因型频率与Ɛ3、Ɛ4等位基因频率,在脑梗死组别中高于对照组(P<0.05)。同时,携带Ɛ3等位基因患者的低密度脂蛋白水平高于携带Ɛ2、Ɛ4等位基因的患者;进一步分析发现含Ɛ3等位基因的脑梗死患者NIHSS评分更高、卒中后认知障碍更严重(P<0.05)。结论 ApoE基因型为Ɛ3/4、等位基因Ɛ3、Ɛ4更易罹患大动脉粥样硬化型脑梗死,提示该基因型是脑梗死的易感基因,脑梗死后认知障碍患者Ɛ3等位基因的频率较高,可能是卒中后认知障碍的易感因素。
Objective To explore the relationship between ApoE gene polymorphisms and post-stroke cognitive impairment,the severity of large artery atherosclerotic cerebral infarction.Methods A case-control research study was conducted,gathering data from 100 individuals diagnosed with large artery atherosclerotic cerebral infarction according to the TOAST classification,who admitted to the Neurology Department of the Affiliated Hospital of Jiujiang University.Additionally,50 non-ischemic stroke patients,matched for gender and age,were included as the control group.The patients were assessed for ApoE genotype,blood lipid,NIHSS,and MMSE scale at 6 months post-stroke,and statistical methods were used to analyze their associations.Results Significant differences were observed in the ApoE 3/4 genotype frequency and Ɛ3、Ɛ4 allele frequency between patients with cerebral infarction and the control group,with a notably higher incidence of cerebral infarction in the former.Furthermore,patients carrying the Ɛ3 allele exhibited significantly higher LDL levels than those carrying Ɛ2 or Ɛ4.The analysis also revealed that patients with the Ɛ4 allele experienced higher NIHSS and severer post-stroke cognitive impairment.Conclusions The findings suggest that the ApoE genotype Ɛ3/4 and allele Ɛ3、Ɛ4 may predispose individuals to develop large atherosclerotic cerebral infarction,indicating a susceptibility gene for cerebral infarction.Additionally,the Ɛ3 allele was associated with a higher frequency of cognitive deficits after cerebral infarction,implying that it may be a predisposing factor for post-stroke cognitive impairment.
目的 探讨载脂蛋白E(ApoE)基因多态性与卒中后认知障碍的相关性,即大动脉粥样硬化型脑梗塞的严重程度。方法 采用病例——对照研究的方法,收集九江学院附属医院神经内科的100例急性缺血性脑卒中且病因分型为大动脉粥样硬化型患者(脑梗死组)和50例性别、年龄匹配的非缺血性脑卒中患者(对照组)。检测患者的 ApoE 基因型、血脂、美国国立卫生院卒中量表(NIHSS)、卒中后6个月简易智力状态检查量表(MMSE)等,采用多因素方差分析等统计学方法分析他们之间的关联性。结果 ApoE 3/4基因型频率与Ɛ3、Ɛ4等位基因频率,在脑梗死组别中高于对照组(P<0.05)。同时,携带Ɛ3等位基因患者的低密度脂蛋白水平高于携带Ɛ2、Ɛ4等位基因的患者;进一步分析发现含Ɛ3等位基因的脑梗死患者NIHSS评分更高、卒中后认知障碍更严重(P<0.05)。结论 ApoE基因型为Ɛ3/4、等位基因Ɛ3、Ɛ4更易罹患大动脉粥样硬化型脑梗死,提示该基因型是脑梗死的易感基因,脑梗死后认知障碍患者Ɛ3等位基因的频率较高,可能是卒中后认知障碍的易感因素。
Objective To explore the relationship between ApoE gene polymorphisms and post-stroke cognitive impairment,the severity of large artery atherosclerotic cerebral infarction.Methods A case-control research study was conducted,gathering data from 100 individuals diagnosed with large artery atherosclerotic cerebral infarction according to the TOAST classification,who admitted to the Neurology Department of the Affiliated Hospital of Jiujiang University.Additionally,50 non-ischemic stroke patients,matched for gender and age,were included as the control group.The patients were assessed for ApoE genotype,blood lipid,NIHSS,and MMSE scale at 6 months post-stroke,and statistical methods were used to analyze their associations. Results Significant differences were observed in the ApoE 3/4 genotype frequency and Ɛ3、Ɛ4 allele frequency between patients with cerebral infarction and the control group,with a notably higher incidence of cerebral infarction in the former.Furthermore,patients carrying the Ɛ3 allele exhibited significantly higher LDL levels than those carrying Ɛ2 or Ɛ4.The analysis also revealed that patients with the Ɛ4 allele experienced higher NIHSS and severer post-stroke cognitive impairment.Conclusions The findings suggest that the ApoE genotype Ɛ3/4 and allele Ɛ3、Ɛ4 may predispose individuals to develop large atherosclerotic cerebral infarction,indicating a susceptibility gene for cerebral infarction.Additionally,the Ɛ3 allele was associated with a higher frequency of cognitive deficits after cerebral infarction,implying that it may be a predisposing factor for post-stroke cognitive impairment.