老年大鼠脑室注射β-淀粉样蛋白1-40单体后吸入异氟烷和七氟烷对海马p-CaMKⅡ及p-CREB表达的影响  

Effect of Isoflurane and Sevoflurane on Hippocampal p-CaMKⅡ and p-CREB Expression after Aged Rats' Encephalocoele Injected with β-amyloid Protein Monomers

作　　者：刘永哲[1] 高明龙[1] 潘宁玲[1] 张宏[2] 

机构地区：[1]北京军区总医院麻醉科,北京100700 [2]解放军总医院麻醉手术中心,北京100853

出　　处：《临床误诊误治》2010年第9期801-804,共4页Clinical Misdiagnosis & Mistherapy

基　　金：国家自然科学基金资助项目(3057192)

摘　　要：目的研究老年大鼠脑室注射β-淀粉样蛋白1-40(Aβ1-40)单体后吸入异氟烷或七氟烷对海马磷酸化钙/钙调蛋白依赖性蛋白激酶Ⅱ(p-CaMKⅡ)和磷酸化cAMP反应结合蛋白(p-CREB)表达水平的影响。方法选择80只20月龄的雄性老年SD大鼠,随机分为8组,每组各10只。对照组脑室注射0.9%氯化钠注射液,实验1组脑室注射Aβ1-40单体,实验2组脑室注射可溶性Aβ1-40寡聚体,实验3组脑室注射不溶性纤维状Aβ1-40,实验4组脑室注射0.9%氯化钠注射液后吸入异氟烷,实验5组脑室注射Aβ1-40单体后吸入异氟烷,实验6组脑室注射0.9%氯化钠注射液后吸入七氟烷,实验7组脑室注射Aβ1-40单体后吸入七氟烷。2周后各组断头取海马,采用Western-blot生物学技术,检测海马p-CaMKⅡ及p-CREB表达水平。结果与对照组比较,实验1组海马p-CaMKⅡ和p-CREB含量差异无统计学意义(P>0.05),实验2、3、4、5、6、7组海马p-CaMKⅡ和p-CREB含量均明显降低(P<0.05)。与实验2组比较,实验5组海马p-CaMKⅡ和p-CREB均显著降低(P<0.05),实验7组海马p-CaMKⅡ含量差异无统计学意义(P>0.05),而p-CREB明显降低(P<0.05)。与实验4组比较,实验5组p-CaMKⅡ和p-CREB含量均明显降低(P<0.05)。与实验6组比较,实验7组p-CaMKⅡ和p-CREB含量均明显降低(P<0.05)。结论异氟烷和七氟烷可通过促进Aβ1-40单体产生神经毒性,引起老年大鼠海马与认知功能相关信号传导系统的抑制。Objective To investigate effect of isoflurane and sevoflurane on hippocampal p-CaMKⅡ and p-CREB expression after aged rats＇ encephalocoele injected with β-amyloid protein 1-40（Aβ1-40） monomers.Methods 80 SD male rats of 20 months old were randomly divided into 8 groups respectively（n=10 in each group）.All groups were given encephalocoele injection,with 0.9% sodium chloride injection in the control group,experimental group 4 and experimetal group 6;with Aβ1-40 monomer in experimental group 1,5 and 7;with soluble Aβ1-40 oligomers in experimental group 2 and with fibrous insoluble Aβ1-40 in experimental group 3.After intraventricular injection,experimental group 4 and experimental group 5 inhaled Isoflurane,experimental group 6 and experimental group 7 inhaled sevoflurane.All groups were killed after two weeks and the hippocampus was isolated to determine the expression of p-CaMKⅡ and p-CREB with Western-blot technique.Results The content of hippocampus p-CaMKⅡ and p-CREB of experimental group 1 showed no significant differences when compared with that of the control group（P0.05）,but were significantly lower in experimental group 2,3,4,5,6 and 7（P0.05）.The content of hippocampus p-CaMKⅡ and p-CREB of experimental group 5 were significantly lower when compared with that of experimental group 2（P0.05）,but in experimental group 7,hippocampus p-CaMKⅡ content showed no significant change（P0.05）,while p-CREB content was significantly lower（P0.05）.When compared with that of experimental group 4,the content of hippocampus p-CaMKⅡ and p-CREB of experimental group 5 were significantly lower（P0.05）.The content of hippocampus p-CaMKⅡ and p-CREB of experimental group 7 were significantly lower than that of experimental group 6（P0.05）.Conclusion Isoflurane and sevoflurane can facilitate the neurotoxicity produced by Aβ1-40 monomer,then extensively suppress aged rats＇ hippocampus cognitive function which is related to signal transduction.

关 键 词：异氟烷 七氟烷 注射 脑室内 β-淀粉样蛋白1-40 大鼠 海马 钙/钙调蛋白依赖性蛋白激酶Ⅱ cAMP反应结合蛋白 

分 类 号：R614[医药卫生—麻醉学]