微量Aβ_(1-40)诱导的α3、α7烟碱型乙酰胆碱能受体的低表达(一种老年性痴呆细胞模型)  

Decreased expression of α3 and α7 nicotinic acetylcholine receptorsbyAβ_(1-40) in PC12 cells

作　　者：田建英[1] 张晓 官志忠 袁万斌[1] 

机构地区：[1]宁夏医学院解剖教研室,银川宁夏750004 [2]Karolinska Institute Dept of NEUROTEC

出　　处：《中风与神经疾病杂志》2004年第4期344-346,共3页Journal of Apoplexy and Nervous Diseases

基　　金：宁夏自治区自然科学基金资助项目(2 0 1号 C12 4);国家教育部优秀青年教师资助项目(教人司 2 0 0 2年 3 5 0号)

摘　　要：目的　探讨老年痴呆症 ( AD)患者大脑中 ,大量神经元烟碱型胆碱能受体 ( n ACh Rs)丢失是否与 β-淀粉样多肽 ( Aβ)沉淀的关系及其影响 n ACh Rs表达的机制 ,建立一种老年性痴呆早期研究离体模型。方法　采用MTT、Annexin- V、配体结合实验以及 Western Blot、RPA法 ,观察 PC12细胞在 Aβ侵害早期 ,细胞损伤机制。结果　显示用纳摩尔浓度 Aβ1 - 40 能明显降低 PC12细胞 [1 2 5I]α- Bungarotoxin和 [3H]Epibatidine结合位点数量 ,引起 α3、α7和 β2亚单位蛋白和 α3、α7m RNA水平的下降 ,但不诱导凋亡 ,却明显抑制 MTT。结论　 Aβ引起的 n ACh Rs生物合成降低 ,可能部分归因于细胞内在信号传导系统。本研究提示 ,在 AD病程早期大量 Aβ纤维形成之前 ,Aβ可直接引起 n Ach Rs退行性改变。应用药物修复 n ACh Rs,干预 Aβ对 n ACh R,尤其是对 α7n ACh R的毒性作用是预防和治疗Objective Few experimental evidence have shown that exposure to Aβ candecrease expression of nicotinic acetylcholineergic receptors(nAChRs).The study is to detect the relationship between the common pathological features of β-amyloid peptide (Aβ) deposition andcholinergic degeneration observed in AD and underling mechanisms.Methods MTT,Annexin-V,binding assay,Western Blot and RPA were taken.Results Treatment with Aβ 1-40 atnanomolar concentrationssignificantly decreased the[ 3H]epibatidine and[ 125 I]α-bungarotoxin binding sites, the protein and mRNA levels of nAChRα3,α7 and β2 subunits in PC12 cells decreased Aβ 1-40 at the concentrations used in the treatment study did not induced apoptosis, but significantlyinhibited the MTT reduction. Conclusion These data suggest thatthe decreased biosynthesis of nAChRs induced by Aβ may be attributable partially to disruption of some intracellular signaling pathways. The results from this study lead to a hypothesis that Aβ can degenerate nAChRs in the early courseof AD before the formation of abundant Aβ fibrils.

关 键 词：AΒ1-40 α3蛋白 α7蛋白 烟碱型乙酰胆碱能受体 老年性痴呆 Β-淀粉样多肽 

分 类 号：R749.16[医药卫生—神经病学与精神病学]