首页|天麻素对急性神经炎症大鼠学习记忆的改善及机制初探

天麻素对急性神经炎症大鼠学习记忆的改善及机制初探

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目的 通过天麻素(GAS)干预急性神经炎症大鼠,观察GAS对大鼠学习记忆能力的改善并探讨其作用机制。方法 50只成年SD雄性大鼠按随机数字法分为3组,即:空白组(Con组,n=10),LPS组(L组,n=20),LPS+GAS组(L+G组,n=20)。Con组大鼠单次腹腔注射生理盐水;L组单次腹腔注射5 mg/kg脂多糖(LPS)建立急性神经炎症模型;L+G组在腹腔注射LPS后给予GAS灌胃,剂量为30 mg/kg。根据LPS作用时间和GAS灌胃频次的不同,L组和L+G组进一步分为7 d、14 d2个亚组(每组n=10)。所有大鼠分别进行如下实验:(1)建模前行5 d Morris水迷宫(MWM)的定位航行实验(PNT),建模后行MWM的空间探索实验(SPT);(2)酶联免疫吸附法(ELISA)检测大鼠海马组织IL-1β、TNF-α的表达;(3)免疫组化法检测大鼠海马区Tau、P-Tau(Ser202)和Aβ蛋白的表达。结果 (1)行为学影响建模前各组大鼠逃避潜伏期逐渐缩短(P<0。05)。建模后,L7 d组、L14 d组大鼠平台穿越次数、有效区域穿越次数、原平台象限穿越次数百分比及滞留时间百分比明显降低(P<0。05),(L+G)7 d组原平台象限穿越次数百分比降低(P<0。05);给予GAS处理后,(L+G)14 d组平台穿越次数、有效区域穿越次数及滞留时间百分比较L14 d组增加(P<0。05)。(2)炎症因子TNF-α、IL-1β的表达与Con组比较,L7 d组、(L+G)7 d组、L14 d组大鼠海马组织炎症因子TNF-α、IL-1β表达升高(P<0。05),(L+G)14 d组海马组织炎症因子IL-1β表达升高(P<0。05);与L14 d组比较,(L+G)14d组TNF-α、IL-1β表达减少(P<0。05)。(3)Tau、P-Tau(Ser202)和Aβ蛋白的表达与Con组比较,L7 d组海马内Tau、Aβ蛋白表达增加(P<0。05),L14 d组海马内Tau、P-Tau、Aβ蛋白表达增加(P<0。05);GAS干预后,(L+G)14 d组海马内P-Tau、Tau、Aβ蛋白表达较L14 d组下降(P<0。05)。结论 GAS可改善急性神经炎症大鼠的空间学习记忆,其机制可能与抗炎、抑制Tau蛋白磷酸化及减少Aβ蛋白沉积有关。
Improvement and mechanism of gastrodin on learning and memory in acute neuroinflammation rats
Objective To observe the improvement effect of Gastrodin(GAS)on the neurocognitive function in rats with acute neuroinflammation and explore its mechanism.Methods Fifty adult SD male rats were randomly divided into three groups,blank group(Con group,n=10),LPS group(L group,n=20),and LPS+GAS group(L+G group,n=20).The rats of the Con group were injected intraperitoneally with saline;the L group was injected intraperitoneally with lipopolysaccharide(LPS)at a dose of 5 mg/kg to establish an acute neuroin-flammation model;the L+G group was given GAS at a dose of 30 mg/kg by gavage after intraperitoneal injection of LPS.The L and L+G groups were further divided into two subgroups of 7 d and 14 d according to the dura-tion of LPS action and frequency of GAS gavage(n=10).The following experiments were performed respective-ly:(1)Place navigation test(PNT)with 5 d Morris water maze(MWM)before model construction,and spatial probe test(SPT)with MWM after modeling;(2)Detect the levels of IL-1 β and TNF-α in rat hippocampal tis-sue by ELISA.(3)Immunohistochemistry was used to detect the expression of Tau,P-Tau(Ser202),and Aβproteins in rat hippocampus.Results(1)Behavioral tests:Before modeling,the escape latency of rats in each group was gradually shortened(P<0.05).After the model was successfully constructed,the number of plat-form traversals,the number of effective area traversals,the percentage of target quadrant traversals,and the per-centage of retention time of the rats in the L7 d an d L14 d groups were significantly reduced(P<0.05),and the percentage of target quadrant traversals in the(L+G)7 d group was reduced(P<0.05);after GAS ga-vage,the number of platform traversals,the number of effective area traversals,and the percentage of retention time of the rats in the(L+G)14 d group were increased(P<0.05)compared with the L14 d group.(2)Com-pared with the Con group,the hippocampal tissue expression of inflammatory factors TNF-α and IL-1 β was ele-vated in the L7d,(L+G)7 d,and L14 d groups of rats(P<0.05),and the hippocampal tissue expression of inflammatory factor IL-1 β was elevated in the(L+G)14 d group(P<0.05).Compared with the L14 d group,TNF-α and IL-1 β expression was reduced in the(L+G)14 d group(P<0.05).(3)Compared with the Con group,Tau and Aβ protein expression was increased in the hippocampus of the L7 d group(P<0.05),and Tau,P-Tau,and Aβ protein expression was increased in the L14 d group(P<0.05).After GAS gavage,the expression of P-Tau,Tau,and Aβ proteins in the(L+G)14 d group was decreased compared with the L14 d group(P<0.05).Conclusion GAS can improve neurocognitive function in rats with acute neuroinflammation,and the mechanism may be related to anti-inflammation,inhibition of Tau protein phosphorylation,and reduction of Aβ protein deposition.

gastrodinacute neuroinflammationcognitive functionmemory

龚涛武、郑雪、石露、朱宇航、吴振宇、张超、朱昭琼

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遵义医科大学附属医院麻醉科,贵州遵义 563003

遵义市妇幼保健院麻醉科,贵州遵义 563003

浙江省人民医院毕节医院麻醉科,贵州毕节 551700

遵义医科大学麻醉医学院,贵州遵义 563006

遵义医科大学附属医院早期临床研究病房,贵州遵义 563003

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天麻素 急性神经炎症 认知功能 记忆

遵义市科技计划资助项目遵义市科技计划资助项目遵义医科大学第三批"12345"未来临床名医

遵市科合HZ202189号遵市科合HZ字2023354号

2024

遵义医科大学学报
遵义医科大学

遵义医科大学学报

CSTPCD
ISSN:2096-8159
年,卷(期):2024.47(10)