摘要：
Objective It is to investigate the cause of propofol combined with ketamine anesthesia juvenile rat hippocampal neurons and cognitive dysfunction in hippocampal tissue proteomic changes, revealing changes in the pathogenesis of hipp-ocampal neurons,providing guidance for improving clinical anesthesia safety .Mtehods 80 rats after birth 7d were divided into saline group ( N group) , ketamine group ( K group) , propofol+ketamine group ( P+K group) low and high dose group chil-dren anesthesia simulation and carried hippocampus and hippocampal slices protein extraction , two-dimensional electropho-resis applications and matrix assisted laser desorption/ionization-time of flight mass spectrometry ( MALDI-TOF) proteomic differences between studies.Results The water maze reaction spell cognitive function; N hippocampal neuronal apoptosis in-dex, K group, compared with the N group (P<0.01), significant statistical significance, while the P +K group and K group was significantly lower compared to the significantly reduced apoptosis (P<0.05), but the low -dose group P +K is still high compared with the N group, the difference was significant (P<0.05), and P +K high dose groups was not signifi-cant.K hippocampal tissue protein concentration , and the NS group,compared with a significant difference.P +K and K group compared with the group with an increasing trend compared with the N -group difference was not significant.K +P group to detect protein in the hippocampus 6h, raised protein found and identified as PD1A3, NDUFB10, HSPA8, ATP5JD, PSMA1, reduced protein PPIA, PKM2, GFAP, NSE, PPIA, PKM2, GFAP and other test results after expressing 21d regula-ted protein FUBP3, PRDX5, down protein GAPDH, AKR1A1, VCP.Conclusion In this study, a preliminary screening tech-nique in proteomics propofol and ketamine anesthesia differentially expressed in hippocampal tissue protein, in order to im-prove the prevention and changes in cognitive function in hippocampal neurons provide a theoretical basis for damages .%目的：探讨异丙酚复合氯胺酮麻醉引起幼年大鼠海马神经元以及认知功能损害后海马组织蛋白组学的变化，了解异丙酚脑保护作用的机制。方法将出生后7 d幼鼠80只随机分为生理盐水组、氯胺酮组、氯胺酮＋异丙酚低剂量组、氯胺酮＋异丙酚高剂量组，除生理盐水组外，其余组均每隔2 h给予相应药物腹腔注射1次，连续给药3次后，每组处死10只大鼠进行大脑海马组织切片及海马蛋白提取，应用MALDI－TOF指纹图谱检测系统进行蛋白组学差异研究。各组剩余的10只大鼠进行水迷宫实验，之后处死进行海马蛋白检测。结果在3d时，氯胺酮组潜伏期显著高于生理盐水组，穿环次数显著低于生理盐水组；氯胺酮＋异丙酚低剂量组和氯胺酮＋异丙酚高剂量组潜伏期明显低于氯胺酮组，氯胺酮＋异丙酚高剂量组明显低于氯胺酮＋异丙酚低剂量组；氯胺酮＋异丙酚低剂量组和氯胺酮＋异丙酚高剂量组穿环次数显著高于氯胺酮组，氯胺酮＋异丙酚高剂量组与生理盐水组和氯胺酮＋异丙酚低剂量组比较差异均无统计学意义。氯胺酮组海马神经元凋亡指数明显高于生理盐水组，氯胺酮＋异丙酚低剂量组和氯胺酮＋异丙酚高剂量组均明显低于氯胺酮组，但氯胺酮＋异丙酚低剂量组仍明显高于生理盐水组，氯胺酮＋异丙酚高剂量组与生理盐水组比较差异无统计学意义。氯胺酮组海马组织蛋白浓度明显低于生理盐水组，氯胺酮＋异丙酚低剂量组和高剂量组与氯胺酮组相比差异均无统计学意义。氯胺酮＋异丙酚组在末次给药后检测海马组织蛋白，发现上调蛋白并鉴定为PD1A3、NDUFB10、HSPA8、ATP5JD、PSMA1、isoform－CRA －c，下调蛋白为PPIA、PKM2、GFAP、NSE、SYN1；21d后检测结果表达上调蛋白为FUBP3、PRDX5，下调蛋白为GAPDH、AKR1A1、VCP、TUBULIN A1 B。结论本实验中蛋白质组学技术初步筛选了异丙酚及氯胺酮麻醉后海马组织蛋白的差异表达，为预防和改善海马神经元变化后认知功能损害提供了理论基础。
