胰岛素对1-甲基-4-苯基吡啶离子诱导的嗜铬细胞瘤细胞损伤的保护

目的 观察胰岛素处理是否减轻1-甲基4-苯基吡啶离子(MPP+)诱导的嗜铬细胞瘤PC12细胞凋亡,探讨可能的机制.方法 测定不同处理后PC12细胞的存活和细胞凋亡情况,观察胰岛素处理对细胞内信号蛋白激酶B(Akt)、糖元合成酶激酶3β(GSK3β)和微管相关蛋白tau磷酸化的影响.结果 胰岛素处理能保护细胞,增加撤除血清后细胞的活力(P＜0.01);增强PC12细胞对100μmol/L MPP+毒性的耐受(P＜0.05),这一作用可以被Akt抑制剂--LY294002阻断.Hoechest染色和流式细胞检测显示,胰岛素干预减少细胞凋亡.100 nmol/L胰岛素处理细胞,Akt ser-473磷酸化程度升高(P＜0.01);GSK3βser-9磷酸化增强(P＜0.01).胰岛素干预,减少tau pS199过磷酸化,而不改变tan pT231的磷酸化.结论 胰岛素通过其细胞内信号通路,调节Akt/GSK3β的磷酸化,减轻MPP+诱导的PC12细胞凋亡.     

胰岛素对百草枯诱导的PC12细胞的保护作用

Objective To observe dopamine (DA) D2R protein expression in the cultured PC 12 cells and the effect of insulin on the survival rate,morphology,and DA of paraquat (PQ)-induced PC12 cells. Methods Immunoprecipitate Western blotting method was performed to observe DA D2R protein expression in PC 12 cells,MTT assay was used to analyze the changes in viability and morphology of PC 12 ceils which were exposed to different concentrations of PQ and insulin. Results (1) DA D2R protein was expressed in PC 12 ceils. (2) Normal PCI2 cells bodies showed fusiform shape and the synapses were in-tegrity. The cells which were exposed to the 600 μmol/L PQ became ball-like, vacuolar degeneration oc-urred,and the synapse became shorter or disappeared. But the morphology of PC12 cells had a little difference between the normal PC12 and the insulin groups,except that the cells were fusiform shape or a-nomalism but not round shape,and the synapses grew. (3) With the increase of the concentration of PQ, the viability of the cells was decreased. Insulin increased the viability of the ceils which were exposed to 600 μmol/L PQ. Insulin elevated DA concentration both in the normal PC12 cells and those exposed to 600 μmol/L PQ,but there was no significant difference ( P > 0.05 ). Conclusion Insulin could protect the PC12 dopaminergic neurons from injury induced by PQ.     

~(11)C-CFT PET显像评价帕金森病与多系统萎缩P型患者脑内多巴胺转运体分布特点的研究

目的基于~(11)C-CFT正电子发射计算机断层(PET)显像评价帕金森病(PD)与多系统萎缩P型(MSA-P)患者脑内多巴胺转运体(DAT)分布特点,评估~(11)C-CFT PET显像在PD与MSA-P鉴别诊断中的价值。方法回顾性分析年龄、性别和疾病严重程度匹配的32例MSA-P患者(MSA-P组)和56例PD患者(PD组)的临床资料以及~(11)C-CFT PET影像资料;另选择年龄匹配的健康对照者20例为对照组。应用感兴趣区技术获得3组研究对象的尾状核、前壳核和后壳核的DAT分布半定量值,对各感兴趣区的DAT分布半定量值、相互比值和不对称性进行对比研究。建立受试者工作特征曲线(ROL),利用曲线下面积评估基于~(11)C-CFT PET显像所得相关参数对PD和MSA-P的鉴别能力。结果与PD组比较,MSA-P组患者病程更短、进展速度更快(P0.000 1)。与对照组比较,PD组和MSA-P组尾状核、前壳核和后壳核的DAT分布半定量值均显著减低(P0.000 1),且后壳核降低最为显著。PD组和MSA-P组尾状核、前壳核和后壳核的DAT分布半定量值及其不对称指数比较均差异无显著性。PD组和MSA-P组纹状体各感兴趣区DAT分布半定量值中,前壳核/尾状核比值(AP/C)、后壳核/前壳核比值(PP/AP)均差异无显著性;但MSA-P组后壳核/尾状核比值(PP/C)PD组(P0.05),两组PP/C比值的ROL曲线下面积为0.696(P=0.002);以0.611作为PP/C比值的临界值,其对MSA-P和PD鉴别诊断的灵敏度和特异度分别为71.9%和62.5%。结论 ~(11)C-CFT PET显像可以精准显示MSA-P及PD患者脑内多巴胺能神经元的突触前功能损害,但尚不能有效鉴别两种疾病。     

视神经脊髓炎谱系疾病免疫靶向药物治疗研究进展

视神经脊髓炎谱系疾病是一种抗体介导的获得性自身免疫性疾病。近年,多种免疫靶向药物被批准用于治疗视神经脊髓炎谱系疾病。因为疗效确切,靶向性特异性免疫治疗极大的改变了视神经脊髓炎谱系疾病患者的预后。本文将从靶点、疗效、不良反应等方面综述靶向性特异性免疫治疗进展。     

胰岛素对百草枯诱导损伤PC12细胞的保护机制的研究

目的 探讨胰岛素对百草枯(PQ)诱导损伤的多巴胺能神经元PC12细胞保护作用的可能机制.方法 在前期实验证明胰岛素对PQ诱导损伤的PC12细胞具有保护作用的基础上,应用免疫沉淀Western印迹分析技术检测空白对照PC12细胞组、PQ干预PC12细胞组(PQ组)、胰岛素干预PC12细胞组(胰岛素组)和PQ与胰岛素共同干预PC12细胞组(胰岛素+PQ组)INRTyr~(1162/1163)和AktSer~(473)磷酸化蛋白的表达情况.结果 免疫沉淀Western印迹分析技术显示:胰岛素组和胰岛素+PQ组通道上出现了表示INRTyr~(1162/1163)磷酸化蛋白表达的棕色带,没有胰岛素干预的通道均未出现棕色带;INR Tyr~(1162/1163)磷酸化蛋白表达量化统计分析显示胰岛素组INRTyr~(1162/1163)磷酸化程度高于胰岛素+PQ组,但差异无统计学意义(P>0.05);而AktSer~(473)磷酸化蛋白表达量化统计分析显示胰岛素组AktSer~(473)磷酸化程度明显高于胰岛素+PQ组,差异有统计学意义(P<0.05).结论 INR Tyr~(1162/1163)磷酸化增加和胰岛素受体后信号传导通路AktSer~(473)磷酸化增加可能是胰岛素保护PQ诱导损伤PC12细胞的机制之一.