CAJ | 학술논문

目的：探讨何首乌二苯乙烯苷（ TSG）对拟痴呆大鼠学习记忆能力及海马组织 CA1区脑啡肽酶（NEP）及低密度脂蛋白相关受体（LRP）-1表达的影响。方法采用随机数字表法将60只大鼠分为 A ~ F 组，每组10只。A 组为对照，背部皮下注射0.9％氯化钠溶液300 mg/ kg，连续6周，1次/ d。B ~ F 组背部皮下注射 D -半乳糖300 mg/ kg 拟阿尔茨海默病（AD）模型，连续6周，1次/ d。造模同时，C 组采用盐酸多奈哌齐0.9 mg/ kg 灌胃，D ~F 组分别给予 TSG 0.05、0.10和0.20 g/ kg 灌胃，连续12周，1次/ d。采用 Morris 水迷宫实验观察大鼠空间记忆能力，前5 d 进行定位航行实验，训练大鼠学习能力，第6天进行空间探索实验，记录大鼠入水角度及穿越平台次数。采用避暗实验观察大鼠被动回避记忆功能，第1天进行训练，24 h 后进行测试，记录5 min 内大鼠进入暗室的次数和潜伏期。大鼠麻醉后眼眶取血，采用放射免疫法检测血清β淀粉样蛋白（Aβ）1-42水平。大鼠处死取脑，采用免疫组化染色，以累计光密度反映海马 CA1区 NEP 和 LRP -1的表达水平。结果各组大鼠入水角度和穿越平台次数比较，差异均有统计学意义（P ﹤0.05）。其中，B 组大鼠入水角度大于 A 组及 C ~ F 组（P ﹤0.05）；B 组穿越平台次数低于 A 组及 C ~ F 组（P ﹤0.05）。各组大鼠潜伏期及遭电击次数比较，差异均有统计学意义（P ﹤0.05）。其中，B 组大鼠潜伏期短于 A 组及 C ~ F 组（P ﹤0.05）；B 组大鼠遭电击次数多于 A、E 组（P ﹤0.05）。各组大鼠血清 Aβ1-42水平及海马 CA1区 NEP、LRP -1累计光密度比较，差异均有统计学意义（P ﹤0.05）。其中，B 组血清 Aβ1-42水平高于 A、E、F 组（P ﹤0.05）；B 组 NEP 累计光密度低于 A 组及 D ~ F 组（P ﹤0.05）；B 组 LRP -1累计光密度低于 A、E 组（P ﹤0.05）。结论何首乌 TSG 可改善拟痴呆大鼠的学习记忆能力，提高大鼠海马组织 CA1区 NEP、LRP -1的表达，增强对 Aβ的降解和转运。目的：探討何首烏二苯乙烯苷（ TSG）對擬癡呆大鼠學習記憶能力及海馬組織 CA1區腦啡肽酶（NEP）及低密度脂蛋白相關受體（LRP）-1錶達的影響。方法採用隨機數字錶法將60隻大鼠分為 A ~ F 組，每組10隻。A 組為對照，揹部皮下註射0.9％氯化鈉溶液300 mg/ kg，連續6週，1次/ d。B ~ F 組揹部皮下註射 D -半乳糖300 mg/ kg 擬阿爾茨海默病（AD）模型，連續6週，1次/ d。造模同時，C 組採用鹽痠多奈哌齊0.9 mg/ kg 灌胃，D ~F 組分彆給予 TSG 0.05、0.10和0.20 g/ kg 灌胃，連續12週，1次/ d。採用 Morris 水迷宮實驗觀察大鼠空間記憶能力，前5 d 進行定位航行實驗，訓練大鼠學習能力，第6天進行空間探索實驗，記錄大鼠入水角度及穿越平檯次數。採用避暗實驗觀察大鼠被動迴避記憶功能，第1天進行訓練，24 h 後進行測試，記錄5 min 內大鼠進入暗室的次數和潛伏期。大鼠痳醉後眼眶取血，採用放射免疫法檢測血清β澱粉樣蛋白（Aβ）1-42水平。大鼠處死取腦，採用免疫組化染色，以纍計光密度反映海馬 CA1區 NEP 和 LRP -1的錶達水平。結果各組大鼠入水角度和穿越平檯次數比較，差異均有統計學意義（P ﹤0.05）。其中，B 組大鼠入水角度大于 A 組及 C ~ F 組（P ﹤0.05）；B 組穿越平檯次數低于 A 組及 C ~ F 組（P ﹤0.05）。各組大鼠潛伏期及遭電擊次數比較，差異均有統計學意義（P ﹤0.05）。其中，B 組大鼠潛伏期短于 A 組及 C ~ F 組（P ﹤0.05）；B 組大鼠遭電擊次數多于 A、E 組（P ﹤0.05）。各組大鼠血清 Aβ1-42水平及海馬 CA1區 NEP、LRP -1纍計光密度比較，差異均有統計學意義（P ﹤0.05）。其中，B 組血清 Aβ1-42水平高于 A、E、F 組（P ﹤0.05）；B 組 NEP 纍計光密度低于 A 組及 D ~ F 組（P ﹤0.05）；B 組 LRP -1纍計光密度低于 A、E 組（P ﹤0.05）。結論何首烏 TSG 可改善擬癡呆大鼠的學習記憶能力，提高大鼠海馬組織 CA1區 NEP、LRP -1的錶達，增彊對 Aβ的降解和轉運。
목적：탐토하수오이분을희감（ TSG）대의치태대서학습기억능력급해마조직 CA1구뇌배태매（NEP）급저밀도지단백상관수체（LRP）-1표체적영향。방법채용수궤수자표법장60지대서분위 A ~ F 조，매조10지。A 조위대조，배부피하주사0.9％록화납용액300 mg/ kg，련속6주，1차/ d。B ~ F 조배부피하주사 D -반유당300 mg/ kg 의아이자해묵병（AD）모형，련속6주，1차/ d。조모동시，C 조채용염산다내고제0.9 mg/ kg 관위，D ~F 조분별급여 TSG 0.05、0.10화0.20 g/ kg 관위，련속12주，1차/ d。채용 Morris 수미궁실험관찰대서공간기억능력，전5 d 진행정위항행실험，훈련대서학습능력，제6천진행공간탐색실험，기록대서입수각도급천월평태차수。채용피암실험관찰대서피동회피기억공능，제1천진행훈련，24 h 후진행측시，기록5 min 내대서진입암실적차수화잠복기。대서마취후안광취혈，채용방사면역법검측혈청β정분양단백（Aβ）1-42수평。대서처사취뇌，채용면역조화염색，이루계광밀도반영해마 CA1구 NEP 화 LRP -1적표체수평。결과각조대서입수각도화천월평태차수비교，차이균유통계학의의（P ﹤0.05）。기중，B 조대서입수각도대우 A 조급 C ~ F 조（P ﹤0.05）；B 조천월평태차수저우 A 조급 C ~ F 조（P ﹤0.05）。각조대서잠복기급조전격차수비교，차이균유통계학의의（P ﹤0.05）。기중，B 조대서잠복기단우 A 조급 C ~ F 조（P ﹤0.05）；B 조대서조전격차수다우 A、E 조（P ﹤0.05）。각조대서혈청 Aβ1-42수평급해마 CA1구 NEP、LRP -1루계광밀도비교，차이균유통계학의의（P ﹤0.05）。기중，B 조혈청 Aβ1-42수평고우 A、E、F 조（P ﹤0.05）；B 조 NEP 루계광밀도저우 A 조급 D ~ F 조（P ﹤0.05）；B 조 LRP -1루계광밀도저우 A、E 조（P ﹤0.05）。결론하수오 TSG 가개선의치태대서적학습기억능력，제고대서해마조직 CA1구 NEP、LRP -1적표체，증강대 Aβ적강해화전운。
Objective To investigage the influence of TSG on the learning and memory and the expression of neprilysin (NEP)and low density lipoprotein receptor 1(LRP - 1)in hippocampus CA1 area of dementia mimetic rats. Methods Using random number table method,60 rats were randomly divided into Group A to Group F,with 10 rats in each group. Group A was the control group which was administrated with 0. 9% and 300 mg/ kg sodium chloride solution by one time per day for 6 weeks consecutively. Group B - F were administrated with back subcutaneous injection of 300 mg/ kg D - galactose by one time per day for 6 weeks consecutively,in order to build AD models. While building models,Group C underwent gavage by 0. 9 mg/ kg donepezil hydrochloride,and Group D - F underwent gavage by TSG of 0. 05,0. 10 and 0. 20 g/ kg respectively by one time per day for 12 weeks consecutively. The space memory ability of the rats were observed by Morris water maze test,during which place navigation test was undertaken in the first 5 days to train the learning ability of rats,and spatial probe test was undertaken on day 6 to record the angel of entering water and the number of times of crossing platform. The memory of passive avoidance was observed by step - through tests,in which the rats were trained on day 1,and tests were conducted 24 hours later with the number of times of entering dark room and latency period recoded within 5 minutes. Blood was sampled from the eye sockets of the rats after anesthesia,and the serum level of Aβ1 - 42 was detected using radioimmunoassay. Brains of the rats were obtained after killing the rats,and after immumohistochemical staining,the expression of NEP and LRP - 1 of hippocampus CA1 area were measured by accumulate optical density. Results The groups were significantly different( P ﹤ 0. 05)in the angle of entering water and the number of times of crossing platform. Group B had bigger angle of entering water than Group A and Group C - F(P ﹤ 0. 05);Group B had lower number of times of crossing platform than Group A and Group C - F(P ﹤ 0. 05). The groups were significantly different(P ﹤ 0. 05)in latency period and the number of times of receiving electric shock. Group B had shorter latency period than Group A and Group C - F(P ﹤ 0. 05);Group B has higher number of times of electric shock than Group A and Group E(P ﹤ 0. 05). The groups were significantly different( P ﹤ 0. 05)in the serum Aβ1 - 42 level and the accumulated optical density of NEP and LRP - 1 in hippocampus CA1 area. Group B was higher than Group A and Group E - F in serum Aβ1 - 42 level(P ﹤ 0. 05);Group B was lower than Group A and Group D - F in the accumulated optical density(P ﹤0. 05);Group B was lower than Group A and Group E in the accumulated optical density of LRP - 1(P ﹤ 0. 05). Conclusion TSG can significantly improve the learning and memory of dementia mimetic ratsm,improve the expression of NEP and LRP -1 in hippocampus CA1 area and promote the degradation and transferring of Aβ.