CAJ | 학술논문

目的研究曲克芦丁对β淀粉样蛋白(Aβ25-35)诱导大鼠AD模型的影响,为AD药物的研发提供实验依据.方法 50只SD大鼠采用随机数字表法分为5组,每组10只,分别为对照组、模型组、曲克芦丁低、中、高剂量治疗组.对照组和模型组给予10 mg/kg体质量5％羧甲基纤维素钠灌胃,曲克芦丁治疗组按不同剂量灌胃给药,低剂量治疗组为10 mg/kg,中剂量组为20mg/kg,高剂量组为50 mg/kg.各组大鼠灌胃14d后,模型组和各剂最曲克芦丁治疗组大鼠双侧海马区注射Aβ25-35 1μL,对照组不做处理.敞箱实验检测各组大鼠运动功能改变情况,Y型迷宫检测各组大鼠认知情况改变情况.比色法测定各组大鼠海马ChAT、AchE的活性,Western blotting检测Bcl和Bax表达水平.结果敞箱实验中,中高剂量治疗组大鼠、垂直水平运动得分均较模型组大鼠明显提高,差异有统计学意义(P＜0.05).Y型迷宫实验中,中高剂量治疗组大鼠正确反应次数较模型组大鼠明显提高,差异有统计学意义(P＜0.05).与模型组相比,高剂量治疗组ChAT活性明显升高,差异有统计学意义(P＜0.05).各组大鼠AchE活性差异无统计学意义(P＞0.05).与模型组比较,中高剂量治疗组Bcl表达明显增加,Bax表达明显降低,差异均有统计学意义(P＜0.05).结论曲克芦丁对Aβ25-35聚集引起的神经毒性具有保护作用,其机制与ChAT活性上调有关.
목적 연구곡극호정대β정분양단백(Aβ25-35)유도대서AD모형적영향,위AD약물적연발제공실험의거.방법 50지SD대서채용수궤수자표법분위5조,매조10지,분별위대조조、모형조、곡극호정저、중、고제량치료조.대조조화모형조급여10 mg/kg체질량5％최갑기섬유소납관위,곡극호정치료조안불동제량관위급약,저제량치료조위10 mg/kg,중제량조위20mg/kg,고제량조위50 mg/kg.각조대서관위14d후,모형조화각제최곡극호정치료조대서쌍측해마구주사Aβ25-35 1μL,대조조불주처리.창상실험검측각조대서운동공능개변정황,Y형미궁검측각조대서인지정황개변정황.비색법측정각조대서해마ChAT、AchE적활성,Western blotting검측Bcl화Bax표체수평.결과 창상실험중,중고제량치료조대서、수직수평운동득분균교모형조대서명현제고,차이유통계학의의(P＜0.05).Y형미궁실험중,중고제량치료조대서정학반응차수교모형조대서명현제고,차이유통계학의의(P＜0.05).여모형조상비,고제량치료조ChAT활성명현승고,차이유통계학의의(P＜0.05).각조대서AchE활성차이무통계학의의(P＞0.05).여모형조비교,중고제량치료조Bcl표체명현증가,Bax표체명현강저,차이균유통계학의의(P＜0.05).결론 곡극호정대Aβ25-35취집인기적신경독성구유보호작용,기궤제여ChAT활성상조유관.
Objective To explore the effect oftroxerutin on β-amyloid(Aβ25-35)-induced AD models,and provide experimental evidence for AD drug development.Methods Fifty SD rats were randomly divided into 5 groups(n=10),namely,normal control group,model group,and low-,mediumand high-dose troxerutin treatment groups.Rats of the normal control group and model group were given sodium carboxymethylcellu lose,and intragastric administration oftroxerutin(10,20 and 50 mg/kg,respectively)was performed on rats of the low-,medium- and high-dose troxerutin treatment groups.Fourteen d after administration of troxerutin,Aβ25-35 at a dosage of 1 μL was injected into the bilateral hippocampus areas of rats in the model group and 3 treatment groups,while rats of the normal control group was not given any treatment.Open field test was employed to detect the motor function changes,and Y-maze test was employed to observe the cognitive function changes; activities of choline acetyltransferase(ChAT) and acetylcholinesterase(AChE) in the hippocampus areas of rats were measured by colorimetric method,and expressions of Bcl and Bax were detected by Western blotting.Results In the open field,the scores of vertical motion in the medium- and high-dose troxerutin treatment groups were significantly higher than those in the model group(P＜0.05); in the Y-maze test,the frequency of correct responses in the medium- and high-dose troxerutin treatment groups was significantly increased as compared with that in the model group(P＜0.05).As compared with that in the model group,the activity of ChAT in the high-dose troxerutin treatment group was obviously increased (P＜0.05); no significant difference on the activity of AchE was noted between each 2 groups(P＞0.05).The expression of Bcl was statistically increased and that of Bax was obviously decreased in the mediumand high-dose troxerutin treatment groups as compared with those in the model group (P＜0.05).Conclusion Troxerutin has a protective effect on Aβ25-35-induced neurotoxicity,whose mechanism may be related to the increase of ChAT activity.