CAJ | 학술논문

目的：探讨阿司匹林对阿尔茨海默病（AD）是否具有防治作用，及是否对相关炎性因子表达存在影响。方法本研究在体内条件下用侧脑室定向注射β淀粉样蛋白（Aβ）25-35模拟AD的基本病理改变，用阿司匹林进行干预，测试大鼠在Morris水迷宫中的逃避潜伏期，并用ELISA检测大鼠脑组织内炎症因子白细胞介素（IL）-6、IL-1β和肿瘤坏死因子α（TNFα）的表达情况。将50只大鼠随机分为5组，每组10只。（1）高剂量阿司匹林干预组：大鼠给予含阿司匹林2g/L的蒸馏水溶液喂服，自由进食。3周后侧脑室内注射Aβ溶液5μl，再予含阿司匹林2g/L的蒸馏水溶液喂服3周，自由进食。（2）中剂量阿司匹林干预组：给予含阿司匹林1g/L的蒸馏水溶液喂服，其余同前。（3）低剂量阿司匹林干预组：给予含阿司匹林0.5g/L的蒸馏水溶液喂服，其余同前。（4）模型组：给予蒸馏水喂服，其余同前。（5）假手术组：给予蒸馏水喂服，3周后侧脑室内注射无菌生理盐水5μl，再予蒸馏水喂服，自由进食。第6周结束时，使用Morris水迷宫测试大鼠学习记忆能力改变。然后处死大鼠使用ELISA方法检测大鼠脑组织内IL-6，IL-1β和TNFα水平。结果（1）阿司匹林各剂量干预组逃避潜伏期较模型组缩短，差异具有统计学意义。（2）IL-1β水平以模型组最高，假手术组最低，各不同阿司匹林剂量干预组水平在前两组之间；而3组阿司匹林干预组中，分别为低剂量组最高，高剂量组最低；差异具有统计学意义。（3）IL-6水平以模型组最高，假手术组最低，阿司匹林各剂量干预组介于两者之间，但总体间差异无统计学意义。（4）TNFα水平以模型组最高，假手术组最低，各不同阿司匹林剂量干预组介于两者之间；各剂量组之间又分别以中剂量组最高，高剂量组最低；差异有统计学意义。结论侧脑室定向注射Aβ25-35能使大鼠学习记忆能力下降。阿司匹林干预可改善AD模型大鼠的学习记忆能力。阿司匹林可能下调IL-1β，IL-6和TNFα等炎症因子的释放，从而对AD模型大鼠学习记忆能力起到保护作用。目的：探討阿司匹林對阿爾茨海默病（AD）是否具有防治作用，及是否對相關炎性因子錶達存在影響。方法本研究在體內條件下用側腦室定嚮註射β澱粉樣蛋白（Aβ）25-35模擬AD的基本病理改變，用阿司匹林進行榦預，測試大鼠在Morris水迷宮中的逃避潛伏期，併用ELISA檢測大鼠腦組織內炎癥因子白細胞介素（IL）-6、IL-1β和腫瘤壞死因子α（TNFα）的錶達情況。將50隻大鼠隨機分為5組，每組10隻。（1）高劑量阿司匹林榦預組：大鼠給予含阿司匹林2g/L的蒸餾水溶液餵服，自由進食。3週後側腦室內註射Aβ溶液5μl，再予含阿司匹林2g/L的蒸餾水溶液餵服3週，自由進食。（2）中劑量阿司匹林榦預組：給予含阿司匹林1g/L的蒸餾水溶液餵服，其餘同前。（3）低劑量阿司匹林榦預組：給予含阿司匹林0.5g/L的蒸餾水溶液餵服，其餘同前。（4）模型組：給予蒸餾水餵服，其餘同前。（5）假手術組：給予蒸餾水餵服，3週後側腦室內註射無菌生理鹽水5μl，再予蒸餾水餵服，自由進食。第6週結束時，使用Morris水迷宮測試大鼠學習記憶能力改變。然後處死大鼠使用ELISA方法檢測大鼠腦組織內IL-6，IL-1β和TNFα水平。結果（1）阿司匹林各劑量榦預組逃避潛伏期較模型組縮短，差異具有統計學意義。（2）IL-1β水平以模型組最高，假手術組最低，各不同阿司匹林劑量榦預組水平在前兩組之間；而3組阿司匹林榦預組中，分彆為低劑量組最高，高劑量組最低；差異具有統計學意義。（3）IL-6水平以模型組最高，假手術組最低，阿司匹林各劑量榦預組介于兩者之間，但總體間差異無統計學意義。（4）TNFα水平以模型組最高，假手術組最低，各不同阿司匹林劑量榦預組介于兩者之間；各劑量組之間又分彆以中劑量組最高，高劑量組最低；差異有統計學意義。結論側腦室定嚮註射Aβ25-35能使大鼠學習記憶能力下降。阿司匹林榦預可改善AD模型大鼠的學習記憶能力。阿司匹林可能下調IL-1β，IL-6和TNFα等炎癥因子的釋放，從而對AD模型大鼠學習記憶能力起到保護作用。
목적：탐토아사필림대아이자해묵병（AD）시부구유방치작용，급시부대상관염성인자표체존재영향。방법본연구재체내조건하용측뇌실정향주사β정분양단백（Aβ）25-35모의AD적기본병리개변，용아사필림진행간예，측시대서재Morris수미궁중적도피잠복기，병용ELISA검측대서뇌조직내염증인자백세포개소（IL）-6、IL-1β화종류배사인자α（TNFα）적표체정황。장50지대서수궤분위5조，매조10지。（1）고제량아사필림간예조：대서급여함아사필림2g/L적증류수용액위복，자유진식。3주후측뇌실내주사Aβ용액5μl，재여함아사필림2g/L적증류수용액위복3주，자유진식。（2）중제량아사필림간예조：급여함아사필림1g/L적증류수용액위복，기여동전。（3）저제량아사필림간예조：급여함아사필림0.5g/L적증류수용액위복，기여동전。（4）모형조：급여증류수위복，기여동전。（5）가수술조：급여증류수위복，3주후측뇌실내주사무균생리염수5μl，재여증류수위복，자유진식。제6주결속시，사용Morris수미궁측시대서학습기억능력개변。연후처사대서사용ELISA방법검측대서뇌조직내IL-6，IL-1β화TNFα수평。결과（1）아사필림각제량간예조도피잠복기교모형조축단，차이구유통계학의의。（2）IL-1β수평이모형조최고，가수술조최저，각불동아사필림제량간예조수평재전량조지간；이3조아사필림간예조중，분별위저제량조최고，고제량조최저；차이구유통계학의의。（3）IL-6수평이모형조최고，가수술조최저，아사필림각제량간예조개우량자지간，단총체간차이무통계학의의。（4）TNFα수평이모형조최고，가수술조최저，각불동아사필림제량간예조개우량자지간；각제량조지간우분별이중제량조최고，고제량조최저；차이유통계학의의。결론측뇌실정향주사Aβ25-35능사대서학습기억능력하강。아사필림간예가개선AD모형대서적학습기억능력。아사필림가능하조IL-1β，IL-6화TNFα등염증인자적석방，종이대AD모형대서학습기억능력기도보호작용。
Objective To investigate whether there is preventive and treatment effect of aspirin on the rat model of Alzheimer’s disease (AD) and its influence on the expression of interleukin (IL)-6, IL-1βand tumor necrosis factorα(TNFα) in the models. Methods A total of 50 SD rats were randomly divided into 5 groups: control group, model group, and low-, middle-and high-dosed aspirin groups. After fed with normal saline containing aspirin at 0, 0.5, 1 and 2g/L respectively for the later 4 groups for 3 weeks, the rats model of AD was established by injecting 5 μl amyloid-beta protein 25-35 (Aβ25-35) into the lateral cerebral ventricle followed by another 3 weeks’ aspirin treatment, while those of control was given normal saline at same volume. The escape latency of the rats was tested in Morris water maze, and the levels of IL-6, IL-1β, TNFαin the brain were detected by enzyme linked immunosorbent assay (ELISA). Results The mean escape latency was significantly shorter in the high-, middle- and low-dosed aspirin groups than in the control group. The brain levels of IL-1β was the highest in the model group, the lowest in the control group, and in a decreasing order in the low-, middle- and high-dosed aspirin groups, with significant difference among them. The brain level of IL-6 was in a similar trend as that of IL-1βin the 5 groups, but there was no significant difference among them. The level of TNFα was also the highest in the model group, and the lowest in the control group, and those in the other 3 groups were between the 2 values. Among the 3 aspirin groups, the middle-dosed group had the highest level of TNFα, and the low-dose group had the lowest level, with significant difference between the 2 groups. Conclusion Lateral cerebral ventricle injection of Aβ25-35 causes short-term decrease in learning and memory abilities in rats. Aspirin intervention attenuates the induced decrease in the abilities. It might exert the protective effect on the learning and memory abilities through down-regulating IL-1β, IL-6, and TNFαin the brain.