异氟醚和七氟醚对脑室内注射β-淀粉样蛋白单体的老年大鼠海马内磷酸化JNK P38及tau蛋白的影响  

Effect of isoflurane and sevoflurane on hippocampal expressions of p-JNK, p-P38 and p-tau in aged rats after intracerebroventricular injection of amyloid-beta protein

作　　者：刘永哲[1] 高明龙[1] 张宏[2] 潘宁玲[1] 

机构地区：[1]北京军区总医院麻醉科,100700 [2]解放军总医院麻醉手术中心

出　　处：《中国药物与临床》2009年第7期553-556,共4页Chinese Remedies & Clinics

基　　金：国家自然科学基金(3057192)

摘　　要：目的通过研究脑室内注射β-淀粉样蛋白(Aβ)单体后异氟醚(I)或七氟醚(S)麻醉对老年大鼠海马内磷酸化JNK、P38及tau蛋白表达水平影响。方法80只20个月龄的雄性老年大鼠,随机分为对照组、Aβ1组、Aβ2组、Aβ3组、I+生理盐水(NS)组、I+Aβ1组、S+NS组、S+Aβ1组。麻醉后2周断头取海马,检测海马内PJNK、p-P38及p-tau蛋白表达水平。结果与对照组相比,Aβ2组、Aβ3组、I+NS组、I+Aβ1组和S+Aβ1组p-JNK和p-P38含量均明显升高(P<0.05),S+NS组仅p-P38含量显著增加(P<0.05)。Aβ2组、Aβ3组、I+Aβ1组和S+Aβ1组p-tau为阳性,其余各组均为阴性。结论异氟醚和七氟醚可能通过促进脑内可溶性Aβ1-40单体发生寡聚化生成具有神经毒性的寡聚物,对信号系统产生更加严重的影响。Objective To investigate the effect of Isoflurane and Sevoflurane on hippocampal expressions of pJNK, p-P38 and p-tan in aged rats after intracerebroventricular injection of amyloid-beta protein. Methods Eighty rats at 20 months of life were randomly divided into 8 groups. Intracerebroventrieular injection of 10μl normal saline （control group）, or Aβl-40 monomer （Aβ1 group）, or soluble Aβ1-40 oligomer （Aβ2 group） or insoluble Aβ1-40 fiber （Aβ3 group） was given. Rats in groups I＋NS and I＋Aβ1 inhaled 1.3 MAC isoflurane for 4 h after the injection of NS or Aβ1-40 monomer, while those in groups S＋NS and S＋Aβ1 inhaled 1.3 MAC sevoflurane for 4 h after the injection of NS or Aβl-40 monomer, respectively. The animals were killed after two weeks and the hippoeampus was harvested to deter- mine the expressions of p-JNK, p-P38 and p-tau using Western-blot techniques. Results The expressions of p-JNK and p-P38 was significantly higher in groups Aβ2,Aβ3, I＋NS, I＋Aβ1 and S＋Aβ1 while p-P38 was significantly high- er only in S＋NS （P〈0.05）. The expression of p-tau was positive in groups Aβ2, Aβ3, I＋Aβ1 and S＋Aβ1 but not in others. Conclusion Both isoflurane and sevoflurane may enhance production of neurotoxie substance resulting from oligomerization of soluble Aβ1 in brain tissue, which can lead to even more harmful effects on signaling pathway.

关 键 词：异氟醚 淀粉样蛋白 阿尔茨海默病 

分 类 号：R96[医药卫生—药理学]