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.
出处
《中国药物与临床》
CAS
2009年第7期553-556,共4页
Chinese Remedies & Clinics
基金
国家自然科学基金(3057192)
