羟基积雪草苷干预神经元退变的机制研究  

The mechanism of interfere effects of madecassoside(MC) on neurodegeneration in mice

作　　者：白洁如[1] 刘颖菊[1] 宋昀[1] 孙峰[1] 高丽佳[1] 

机构地区：[1]重庆医科大学药学院药理教研室,重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国老年学杂志》2008年第23期2297-2300,共4页Chinese Journal of Gerontology

基　　金：重庆市自然科学基金资助(CSTC,2005BB5036)

摘　　要：目的探讨羟基积雪草苷(madecassoside,MC)对慢性铝中毒所致小鼠海马神经元损伤的干预作用及机制。方法按葡萄糖酸铝(400mgAl3+/kg)给予NIH小鼠灌胃90d建立铝中毒神经元损伤小鼠模型。通过跳台和Morris水迷宫实验、生化实验、HE染色和免疫组化染色技术,观察MC大小剂量(每天30、60mg/kg)同步给药90d对小鼠学习记忆能力、脑丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性、海马神经元病理形态学、海马Caspase-3和COX-2蛋白表达的影响。结果与模型组相比,30和60mg/kg剂量MC可明显延长铝中毒小鼠跳台潜伏期(31.40±22.04vs124.10±74.38和138.80±90.85)(P<0.05),减少跳台错误次数(3.00±1.15vs1.60±0.69和1.40±0.84)(P<0.05),缩短第5天寻找平台潜伏期(36.2±11.2vs18.5±7.3和19.4±9.9)(P<0.05)的时间;明显减少脑内MDA含量(nmol/mgprot)(3.73±0.38vs2.50±0.42和2.59±0.47)(P<0.05),提高脑内SOD酶活性(U/mgprot)(362.8±37.6vs445.7±23.9和425.5±38.8);大小剂量的MC均能明显减轻铝中毒小鼠海马神经元损伤,下调海马神经元Caspase-3(0.255±0.079vs0.090±0.026和0.132±0.049)(P<0.05)和COX-2(0.099±0.006vs0.038±0.004和0.045±0.008)(P<0.05)蛋白表达。结论MC可通过提高抗氧化应激、阻遏神经元凋亡和抗炎作用,减轻海马神经元损伤。Objective To study the protective effects and possible mechanisms of madecassoside （MC） on hippocampal neurons in mice. Methods Demented models of mice were made by gavage with A1400 mg · kg^- 1· d^-1 for 90 d. Effects of different MC dosage （30, 60 mg · kg^-1 · d^-1 ） on the following parameters were evaluated by behavioral, biochemical, pathological and immunohistoehemical methods, including behavioral changes of passive learning and memory ability and spatial recognition ability, biochemical changes including levels of malondialdehyde （MDA） and SOD, pathological alterations of hippocampal neurons, as well as protein expression of caspase-3 and COX- 2 in hippocampal neurons. Results MC 30 and 60 mg · kg^-1 · d^-1 for 90 d significantly prolonged the latency （ 31.40 ± 22. 04 vs 124. 10 ±74. 38 and 138. 80 ±90. 85） （P 〈0.05） and reduced the number of errors （3.00 ± 1.15 vs 1.60 ±0. 69 and 1.40 ±0. 84） （P 〈 0.05 ） trained in step-down test and shortened the escape latency （ 36. 2 ± 11.2 vs 18.5 ± 7.3 and 19.4 ± 9. 9 ） （ P 〈 0. 05 ） of demented mice in Morris water maze task, markedly decreased the elevations of MDA levels （ nmol/mg prot） （ 3. 73 ± 0. 38 vs 2. 50 ± 0. 42 and 2. 59 ± 0.47 ） （ P 〈 0. 05 ） and increased the activities of SOD（ U/mg prot） （ 362. 8 ± 37.6 vs 445.7 ± 23.9 and 425.5 ± 38.8 ） （ P 〈 0.05 ） in mice brain. Moreover, both dosages of MC significantly attenuated the damage to hippocampal neurons and inhibited the protein expression of caspase-3 （0. 255 ±0. 079 vs 0. 090 ±0. 026 and 0. 132 ±0. 049） （P 〈0. 05） and COX-2 （0. 099 ±0. 006 vs 0. 038 ±0. 004 and 0. 045 ± 0. 008 ） （ P 〈 0. 05 ） in hippoeampal neurons of demented mice. Conclusions MC can protect hippocampal neurons against injury obviously by enhancing anti-oxidant capacity and preventing neurons from apoptosis and anti-inflammatory effect.

关 键 词：羟基积雪草苷 神经元凋亡 炎症反应 CASPASE-3 COX-2 

分 类 号：R285.5[医药卫生—中药学]