银杏叶提取物对迟发性运动障碍大鼠模型的干预研究

The efficacy of Egb761 on haloperidol-induced tardive dyskinesia model male rats and possible mechanism

目的 观察银杏叶提取物（ginkgo biloba extract,Egb761）对迟发性运动障碍（tardive dyskinesia,TD）模型大鼠行为学和血清脑源性神经营养因子（brain derived neurotrophic factor, BDNF）、总抗氧化能力（total antioxidant capacity,TAC）水平的影响,探索可能的治疗机制.方法 将32只雄性Sprague-Dawley大鼠采用随机数字表法随机分为生理盐水组（腹腔注射生理盐水2 ml/kg＋第5周始灌胃生理盐水5 ml/kg）、TD组（腹腔注射氟哌啶醇2 mg/kg＋第5周始灌胃生理盐水5 ml/kg）、Egb761组（腹腔注射氟哌啶醇2 mg/kg＋第5周始灌胃Egb761溶液5 ml/kg）、VitE组（腹腔注射氟哌啶醇2 mg/kg＋第5周始灌胃VitE溶液5 ml/kg）,每组8只,观察10周.每周第7天评定大鼠空嚼运动（vacuous chewing movements）的严重程度.第10周末采用酶联免疫吸附法检测血清BDNF浓度,采用分光光度法检测TAC水平.结果 （1）空嚼运动比较：与生理盐水组相比,第2周末TD组、Egb761组、VitE组空嚼运动评分显著增加（F=8.96,P＜0.05）,第5周末达峰值;第6周后,Egb761组、VitE组空嚼运动评分逐步下降;第10周末2治疗组空嚼运动评分[（4.1±2.0）、（6.5±3.3）分]显著低于TD组[（27.9±5.8）分]（F=164.44,P＜0.01）,与生理盐水组[（3.5±1.9）分]相比差异无统计学意义（F=1.22,P＞0.05）;（2）BDNF和TAC比较：第10周末,TD组血清BDNF[（6.9±1.0） ng/L]、TAC[（11.9±3.2） mU/L]水平显著低于生理盐水组[（8.6±2.5） ng/L、（18.2±5.5） mU/L]、Egb761组[（8.9±1.5） ng/L、（19.4±4.4） mU/L]和VitE组[（8.7±2.0） ng/L、（18.6±5.9） mU/L],Egb761与VitE治疗后BDNF和TAC水平高于TD组（F=4.21,F=6.67,P＜0.05）,与生理盐水组差异无统计学意义（F=0.25,F=0.88,P＞0.05）;（3）生理盐水组大鼠血清BDNF与TAC水平显著相关（r=0.689,P＜0.05）,另外3组未发现两者存在显著相关.结论 Egb761与VitE均可显著缓解TD模型大鼠空嚼运动症状,神经营养因子降低和自由基代谢异常可能在TD发生过程中作用关键.

Objective To investigate the efficacy of Egb761 on vacuous chewing movements （VCMs） of haloperidol-induced tardive dyskinesia （TD） rats and serum levels of brain-derived neurotrophic factor （BDNF） and total antioxidant capacity （TAC）, and to explore the possible mechanism of treatment. Methods Thirty-two male Sprague-Dawley （SD） rats were randomly divided into the normal saline （NS）, TD, Egb761, vitamin E （VitE） group （n=8）, processed with NS, haloperidol ＋ NS, haloperidol ＋ Egb761, haloperidol ＋ VitE with 8 rats in each group, the test duration was 10 weeks. VCM was evaluated at each weekend. Venous blood was collected at the end of 10th week, and the serum levels of BDNF and TAC were assayed. Results （1）VCM score of TD, Egb761, VitE group increased gradually after two weeks and reached the peak at the 5th weekend, and they were significantly higher compared with that of NS group（F=8.96,P〈0.05）. VCM score of Egb761, VitE group dropped gradually after six weeks. At the 10th weekend, VCM score of the two treated groups （（4.1±2.0）,（6.5±3.3））were lower markedly than that of TD group（27.9± 5.8）, the differences were statistically significant（F=164.44,P〈0.01）,and the comparison of that with NS group（3.5±1.9）had no significance（F=1.22,P〉0.05）;（2）At the 10th weekend, serum BDNF（（6.9±1.0） ng/L）, TAC（（11.9±3.2） mU/L） levels of TD group were significantly lower than that of the NS （（8.6±2.5） ng/L, （18.2± 5.5） mU/L）,Egb761（（8.9 ± 1.5） ng/L, （19.4 ± 4.4） mU/L） and VitE group （（8.7 ± 2） ng/L, （18.6 ± 5.9） mU/L）. Serum BDNF and TAC levels of the two groups were higher than that of TD group（F=4.21,F=6.67,P〈0.05） after treatment with Egb761 or VitE, there were no significant differences among NS, Egb761 and VitE groups（F=0.25,F=0.88,P〉0.05）;（3）BDNF serum concentrations were related to the TAC levels （r=0.689, P〈0.05） in NS group, however, relationships were not found among the other 3 groups. Conclusions Egb761 and VitE could significantly alleviate VCM score in TD model rats, and decreases of the neurotrophic factors and abnormal metabolism of the free radicals might play a role in etiology of TD.