CAJ | 학술논문

目的探讨蓓萨罗丁(BEX)对AD小鼠空间认知、学习记忆损伤及海马神经再生的影响. 方法雄性健康ICR小鼠80只按随机数字表法分为对照组、模型组、BEX低剂量组和BEX高剂量组,每组20只.后3组小鼠采用侧脑室注射Aβ25-35肽段制备AD模型,后2组小鼠均于造模后7d灌胃50、100mg/ (kg·d)的BEX(连续14 d),对照组给予等量生理盐水.造模后28 d采用Morris水迷宫和Y型电迷宫实验分别检测各组小鼠的空间认知、学习记忆功能.各组小鼠于造模后每天腹腔注射5-溴脱氧尿嘧啶核苷(BrdU)3次,连续28 d后采用免疫组化染色检测海马BrdU的表达;双皮层蛋白(DCX)染色检测神经元前体细胞的增殖和迁移;Hoechst染色检测细胞凋亡;甲苯胺蓝染色检测成熟颗粒细胞;ELISA法检测海马脑源性神经营养因子(BDNF)的含量;Westernblotting检测海马胶质原纤维酸性蛋白(GFAP)和生长相关蛋白-43 (GAP-43)的表达. 结果 Morris水迷宫实验第3、4、5、6天对照组、BEX高剂量组、BEX低剂量组、模型组小鼠的逃避潜伏期逐渐增加,第6天4组大鼠站台所在象限停留时间逐渐降低[分别为(33.76±2.87)s、(29.37±2.85)s、(26.68±3.26)s、(21.53±3.63)s];小鼠的正确反应所需电击次数逐渐增加,正确反应次数逐渐减少;海马区BrdU阳性细胞数、DCX阳性神经突起长度、DCX阳性神经突起密度和成熟颗粒细胞数逐渐减少,而Hoechst阳性细胞数逐渐增加;海马BDNF水平、GFAP、GAP-43蛋白表达(分别为0.81±0.28、0.76±0.22、0.62±0.16、0.55±0.11)逐渐降低,差异均有统计学意义(P＜0.05). 结论 BEX可改善AD小鼠的空间认知、学习记忆损伤,并促进其海马神经再生.
목적 탐토배살라정(BEX)대AD소서공간인지、학습기억손상급해마신경재생적영향. 방법 웅성건강ICR소서80지안수궤수자표법분위대조조、모형조、BEX저제량조화BEX고제량조,매조20지.후3조소서채용측뇌실주사Aβ25-35태단제비AD모형,후2조소서균우조모후7d관위50、100mg/ (kg·d)적BEX(련속14 d),대조조급여등량생리염수.조모후28 d채용Morris수미궁화Y형전미궁실험분별검측각조소서적공간인지、학습기억공능.각조소서우조모후매천복강주사5-추탈양뇨밀정핵감(BrdU)3차,련속28 d후채용면역조화염색검측해마BrdU적표체;쌍피층단백(DCX)염색검측신경원전체세포적증식화천이;Hoechst염색검측세포조망;갑분알람염색검측성숙과립세포;ELISA법검측해마뇌원성신경영양인자(BDNF)적함량;Westernblotting검측해마효질원섬유산성단백(GFAP)화생장상관단백-43 (GAP-43)적표체. 결과 Morris수미궁실험제3、4、5、6천대조조、BEX고제량조、BEX저제량조、모형조소서적도피잠복기축점증가,제6천4조대서참태소재상한정류시간축점강저[분별위(33.76±2.87)s、(29.37±2.85)s、(26.68±3.26)s、(21.53±3.63)s];소서적정학반응소수전격차수축점증가,정학반응차수축점감소;해마구BrdU양성세포수、DCX양성신경돌기장도、DCX양성신경돌기밀도화성숙과립세포수축점감소,이Hoechst양성세포수축점증가;해마BDNF수평、GFAP、GAP-43단백표체(분별위0.81±0.28、0.76±0.22、0.62±0.16、0.55±0.11)축점강저,차이균유통계학의의(P＜0.05). 결론 BEX가개선AD소서적공간인지、학습기억손상,병촉진기해마신경재생.
Objective To explore the effect of bexarotene (BEX) on spatial cognition,impairment in memory and learning and hippocampal nerve regeneration of Aβ25-35 mice.Methods Eighty healthy male ICR mice were randomly divided into control group,model group,low-dosage BEX treatment group and high-dosage BEX treatment group (n=20); AD mouse models in the later three groups were induced by intracerebroventricular injection of Aβ25-35; and mice in the low-dosage BEX treatment group and high-dosage BEX treatment group treated with BEX (50 and 100 mg/kg·d) by gavage 7 days after Aβ25-35 injection for consecutive 14 days.Morris water maze and Y-maze tests were used to test the spatial cognitive function and abilities of learning and memory,respectively,28 days after Aβ25-35 injection.Intraperitoneal injection of 5-bromodeoxyuridine (BrdU) three times daily for 28 days was performed,and then,immumohistochemical staining was employed to detect the BrdU expression in the hippocampus; dual cortex protein (DCX) staining and Hoechst staining were,respectively,used to evaluate the proliferation and migration,and apoptosis of neuronal precursor cells; toluidine blue staining was employed to evaluate the mature neurons in the hippocampus.The levels of hippocampal brain-derived neurotrophic factor (BDNF) and the expressions of hippocampal glial fibrillary acidic protein (GFAP) and growth associated protein-43 (GAP-43) were measured by ELISA and Western blotting,respectively.Results Morris water maze test showed that the latency of crossing the platform was gradually increased in the control group,high-dosage BEX treatment group,low-dosage BEX treatment group and model group on the 3nd,4th,5th and 6th day,and the duration of stay was gradually decreased on the 6th day; increased learning frequency and reduced memory frequency was noted in Y-maze test; number of BrdU-positive cells,length and density of DCX neurite,and number of granule cells in the hippocampus decreased gradually,while Hoechst-positive cells decreased gradually; hippocampal levels of GFAP,GAP-43 and BDNF decreased gradually; the differences in the above levels were statistically significant (P＜0.05).Conclusion BEX can improve the spatial cognition and the impairment in memory and learning and promote their hippocampal neurogenesis of Aβ25-35 mice.