胸腺肽a1对小鼠新生期感染所致学习记忆障碍的影响  

Protective effect of thymosin alpha-1 on postnatal systemic inflammation induced learning and memory impairment in mice

作　　者：王阁[1] 余文富[1] 王潇[2] 何芬[3] 邹俊涛[2] 

机构地区：[1]衢州职业技术学院医学院,衢州324000 [2]中山大学中山医学院人体解剖教研室,广州510080 [3]广州医科大学附属第一医院放疗科,广州510120

出　　处：《中华神经医学杂志》2017年第2期121-126,共6页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金（2015A030313153、2014A030310343）;衢州市科技计划项目（2015103）

摘　　要：目的探讨胸腺肽a1对新生小鼠持续感染所致学习记忆障碍的影响及其相关机制。方法（1）新生C57BL／6小鼠24只按随机数字表法分为生理盐水组、0-3mg／kg脂多糖（LPS）剂量组、0．6mg/kgLPS剂量组、0．9mg／kgLPS剂量组，分别连续5d注射等量生理盐水和不同剂量LPS。观察各组小鼠体质量、相对肝重变化及血清、脑组织肿瘤坏死因子-α（TNF-α）含量，以确定模拟临床新生儿感染的LPS剂量。（2）取60只新生小鼠按随机数字表分为3组：对照组、LPS组、胸腺肽a1处理组，分别连续5d注射等量生理盐水、LPS（0．6mg／kg）和胸腺肽a1（0．4mg／kg）＋LPS（0．6mg／kg）。在4周和8周时，采用Morris水迷宫实验检测各组小鼠的学习记忆能力，采用ELISA法检测海马组织TNF-α、白介素-1β（IL-1β）、脑源性神经营养因子（BDNF）和神经生长因子（NGF）含量，采用Western blotting检测海马组织Toll样受体4（TLR4）和核转录因子-κB（NF-κB）蛋白表达水平。结果（1）与生理盐水组相比，0．6mg／kgLPS剂量组小鼠生长缓慢[（2．23±0．22）g vs （1．18±0．21）g]、相对肝重增加（0．052±0．004 vs 0．072±0．007）、血清及脑组织TNF-α含量[（62．01±3．32）pg／mL vs（151．06±14．51）pg／mL；（186．03±13．24）pg／mL vs（298．71±41．61）pg／mL]明显增高，差异均有统计学意义（P〈0．05）。（2）与LPS组相比，胸腺肽a1处理组小鼠定位航行实验中逃避潜伏期明显缩短，空间探索实验中目标象限停留时间明显延长，海马组织TNF-α、IL．1B、TLR4、NF-κB蛋白表达明显降低[（73．32±5．18）pg／mL vs（58．61±4．03）pg／mL；（99．15±8．30）pg／mL vs（75．56±6．13）pg／mL；2．32±0．29 vs 1．71±0．26；1．77±0．24 vs 1．26±0．141，BDNF、NGF蛋白表达明显增高[（1．33±0．12）pg／mL／）8（1．69±0．25）pg／mL；（41．45±3．47）pg／mL vObjective To explore the effect ofthymosin alpha-1 （Tal） on postnatal systemic inflammation-induced learning and memory impairment in mice and their relevant mechanism. Methods （I） Twenty-four neonatal C57BL/6 mice were randomly assigned into normal saline group, lipopolysaccharide （LPS, 0.3 mg/kg） group, LPS （0.6 mg/kg） group, and LPS （0.9 mg/kg） group. And the animals were intraperitoneally injected with different doses of LPS or equal volume of saline for 5 days. The variations of body weight, liver weight relative to the body and tumor necrosis factor-α （TNF-α） level in serum and brain tissues were observed to determine the appropriate dose of LPS for simulating neonatal clinical infection. （2） A total of 60 newborn mice were randomly divided into three groups： control group, LPS group and Tal treatment group; mice in each group were continuously injected with equal volume saline, LPS （0.6 mg/kg） and Tal （0.4 mg/kg）±LPS （0.6 mg/kg） for 5 days. On day 28 and on day 56, Morris water maze was used to measure the spatial learning and memory abilities of mice; the concentrations of TNF-α, interleukin-1β （IL-1β）, brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） in the hippocampus were examined by ELISA, and the expressions of toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） were measured by Western blotting. Results （1） As compared with the normal saline group, the mice in the LPS group （0.6 mg/kg） had significantly slower growth （[2.23±0.22] g vs. [1.18±0.21] g）, increased relative liver weight to the body （0.052±0.004 vs. 0.072±0.007） and increased TNF-α levels in serum and brain tissues （[62.01 ±3.32] pg/mL vs. [151.06± 14.51] pg/mL; [186.03±13.24] pg/mL vs. [298.71±41.61] pg/mL, P〈0.05）. （2） As compared with the LPS group, Tal treatment group had significantly shortened average escape latency in place navigation test, prolonged active time in spatial probe test, statistically d

关 键 词：感染性疾病 胸腺肽A1 学习记忆能力 脑源性神经营养因子 神经生长因 子 TOLL样受体4 核转录因子-ΚB 

分 类 号：R749.94[医药卫生—神经病学与精神病学]