| 吡格列酮对淀粉样β蛋白片段1-42引起的大鼠海马神经细胞凋亡相关蛋白表达的影响 |
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| 引用本文： | 姜艳,金英,王世兴,李亚男,闫恩志,齐志敏,魏佳.吡格列酮对淀粉样β蛋白片段1-42引起的大鼠海马神经细胞凋亡相关蛋白表达的影响[J].中国药理学与毒理学杂志,2008,22(5):355-361. |
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| 作者姓名： | 姜艳 金英 王世兴 李亚男 闫恩志 齐志敏 魏佳 |
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| 作者单位： | 1. 辽宁省辽宁医学院,药理学教研室,辽宁,锦州,121001
2. 辽宁省辽宁医学院科学实验中心,辽宁,锦州,121001 |
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| 摘 要： | 目的研究吡格列酮(Pio)对淀粉样β蛋白片段1-42(Aβ1-42)所致大鼠海马神经细胞凋亡的抑制作用及作用机制。方法大鼠随机分为5组,即正常对照组,Aβ1-42损伤组,Aβ1-42+Pio20,40及80mg·kg-1组。于d1和2,Pio处理组大鼠灌胃给予Pio,正常对照组和Aβ1-42损伤组灌胃给予0.2%二甲亚砜。d2给药处理后,Aβ1-42损伤组及Pio处理组大鼠左侧脑室内单次注射Aβ1-425μL(2.0mmol·L-1)制备大鼠痴呆模型,正常对照组注射等量的生理盐水。再连续给药6d后,取海马CA1区,用Western蛋白印迹法检测半胱氨酸天冬氨酸蛋白酶(caspase)3,caspase7,caspase9及μ-钙蛋白酶和多聚ADP-核糖聚合酶(PARP)蛋白表达水平的变化。结果脑室内注射Aβ1-42可使大鼠海马CA1区活化的caspase3,caspase7,caspase9蛋白及μ-钙蛋白酶表达水平明显增高,分子质量116kuPARP表达明显减少,而分子质量89ku劈切PARP表达明显增加。Pio40及80mg·kg-1可明显抑制Aβ1-42所致海马CA1区活化的caspase9和μ-钙蛋白酶表达增加,也可明显抑制Aβ1-42所致的PARP表达的改变。但Pio20mg·kg-1对Aβ1-42所致海马caspase9,μ-钙蛋白酶和PARP表达无明显作用。Pio20,40及80mg·kg-1均可抑制Aβ1-42所致海马CA1区活化的caspase3和caspase7表达增加。结论Pio对Aβ1-42引起的海马神经细胞凋亡具有明显的抑制作用。
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| 关 键 词： | 吡格列酮 半胱氨酸天冬氨酸蛋白酶 过氧化物酶增殖物活化受体γ 钙蛋白酶 |
| 收稿时间： | 2008-2-18 |
Effects of pioglitazone on amyloid beta-protein fragment 1-42-induced apoptosis-related protein expressions in rat hippocampus |
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| JIANG Yan,JIN Ying,WANG Shi-Xing,LI Ya-Nan,YAN En-Zhi,QI Zhi-Min,WEI Jia.Effects of pioglitazone on amyloid beta-protein fragment 1-42-induced apoptosis-related protein expressions in rat hippocampus[J].Chinese Journal of Pharmacology and Toxicology,2008,22(5):355-361. |
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| Authors: | JIANG Yan JIN Ying WANG Shi-Xing LI Ya-Nan YAN En-Zhi QI Zhi-Min WEI Jia |
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| Affiliation: | (1. Department of Pharmacology, 2. Department of Scientific Experiment, Liaoning Medical University, Jinzhou 121001, China) |
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| Abstract: | AIM To investigate whether the inhibitory effect of pioglitazone(Pio) on amyloid beta-protein fragment 1-42 (Aβ1-42)-induced hippocampal neuron apoptosis. METHODS The rats were randomly divided into 5 groups: normal, Aβ1-42 and Aβ1-42+Pio groups (20, 40 and 80 mg·kg-1, respectively). On d 1 and d 2, the rats of normal, model and Pio groups were given 0.2% DMSO or Pio (ig). On d 2, single dose Aβ1-42 (5 μL, 2 mmol·L-1) were given (icv) to model and Pio groups (after Pio given). Then, the rats of Pio groups were given Pio once daily for 6 d. In the normal group, rats were injected (icv) with the same volume of normal saline. The hippocampal expressions of caspase 3, caspase 7 and caspase 9 proteins and μ-calpain and peroxisome poly ADP-ribose polymerase (PARP) were determined in the brain tissue preparations from CA1 area with Western blot. RESULTSAβ1-42 induced significant increase in activated caspase 3, caspase 7 and caspase 9 protein and μ-calpain expressions and caspase 3 substrate PARP cleavage. Treatment with Pio 40 and 80 mg·kg-1 significantly prevented Aβ1-42-induced increase in expressions of the proapoptotic proteins activated caspase 3, caspase 7, caspase 9 and μ-calpain and changes of PARP cleavage in hippocampal CA1 region. But Pio 20 mg·kg-1 did not abrogated Aβ1-42 induced changes in caspase 9, caspase 3, caspase 7, μ-calpain and PARP protein expressions. CONCLUSION Pio has inhibitive effect on Aβ1-42-induced hippocampal neuron apoptosis in rat hippocampus. |
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| Keywords: | pioglitazone caspases peroxisome proliferator-activated receptor γ calpain |
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