【作者】 郝吉莉；

【导师】 周兰兰；

【作者基本信息】 安徽医科大学 ， 药理学， 2007， 硕士

【摘要】 脑卒中后抑郁(Post stroke depression,PSD)是指脑卒中后引发的抑郁症,是脑卒中后常见并发症。黄蜀葵总黄酮( Total flavone of Abelmoschus manihot L.Medic,TFA)是从锦葵科植物黄蜀葵中提取的一类有效成分,其主要活性成份为金丝桃苷(Hyperin,Hyp )、槲皮素和槲皮素苷。我室前期研究表明TFA和Hyp均具有脑缺血保护作用,其作用机制可能与抗脂质过氧化等有关。但有关TFA抗PSD作用尚未见报道。本课题主要研究TFA抗PSD作用及部分作用机制。主要实验结果如下:1 TFA对PSD大鼠模型的影响采用线栓法阻断右侧大脑中动脉(Middle cerebral artery,MCA)1h后再灌注制备局灶性脑缺血模型,在此基础上复合慢性应激和孤养,制备PSD大鼠模型。术后动态监测大鼠的体重变化,采用敞箱实验观察大鼠的行为学改变,通过糖水消耗量测定检测大鼠对奖赏的反应程度。结果显示,TFA(50,100mg/kg,qd×24d)可不同程度增加PSD大鼠体重,提高水平运动和垂直运动得分,增加糖水消耗量,表明TFA可不同程度地改善PSD大鼠的抑郁状态,使体重相对增加,活动增多,糖水消耗量增加,表现较好的抗抑郁效应。2 TFA的抗脂质过氧化作用应用紫外分光光度计法检测脑组织丙二醛(Malondialdehyde,MDA)含量、超氧化物岐化酶(Superoxide Dismutase,SOD)以及谷胱甘肽过氧化物酶(Glutathioneperoxidase,GSH-Px)活性。结果表明,TFA(50,100mg/kg,qd×24d)能抑制PSD大鼠脑组织中升高的MDA含量,并提高GSH-Px活性;TFA(25,50,100mg/kg,qd×24d)可不同程度提高PSD大鼠脑组织中SOD活性。提示TFA具有抗脂质过氧化作用,这可能与它发挥抗PSD效应密切相关,是重要机制之一。3 TFA对血液流变学的改善作用用R-80锥板型血液流变检测仪测定各切变率下全血粘度、血浆粘度、红细胞压积以及红细胞变形指数。结果显示, TFA(50,100mg/kg,qd×24d)能抑制PSD大鼠中、高切变率下全血粘度的升高,并能显著提高红细胞的变形性;TFA(100mg/kg,qd×24d)能抑制PSD大鼠低切变率下全血粘度和血浆粘度的升高。提示TFA对PSD大鼠的血液流变学具有明显的改善作用,这可能是其抗PSD重要机制之一。4 TFA对下丘脑-垂体-肾上腺(Hypothalamic-pituitary-adrenal,HPA)轴功能的改善作用采用放射免疫分析法检测PSD大鼠血浆ACTH和皮质醇浓度;应用免疫组织化学法检测PSD大鼠下丘脑室旁核(Paraventricular nucleus,PVN)中促肾上腺皮质激素释放激素(Corticotropin releasing factor,CRF)的表达;应用半定量逆转录聚合酶链反应法检测PSD大鼠下丘脑CRFmRNA的表达。结果显示,TFA(25,50,100mg/kg,qd×24d)可不同程度地抑制PSD大鼠血浆ACTH和皮质醇浓度的增高;TFA(50,100mg/kg,qd×24d)可明显降低PSD大鼠PVN中CRF阳性神经元的平均光密度值,并抑制PSD大鼠下丘脑CRFmRNA的过度表达。表明TFA可有效抑制HPA轴的过度激活,这可能是它发挥抗PSD效应的重要机制。结论:TFA对大鼠PSD模型具有明显的抗抑郁作用,其机制可能与其抗脂质过氧化、改善血液流变学以及抑制HPA轴的过度激活有关。更多还原

【Abstract】 Post stroke depression(PSD) is depression that develops after ischemic stroke.It is a common complication of stroke. Total flavone of Abelmoschus manihot L.Medic (TFA) was extracted from Abelmoschus manihot L.Medic. The essential components of TFA are hyperin, quercetin and other flavonoids. Our former studies indicated that TFA and Hyp have protective effects against cerebral ischemia,and its mechanisms may be related to decrease lipid peroxidation. It has not been reported about the antidepressant effects of TFA.This study is intended to investigate antidepressant effects and possible mechanisms of TFA on PSD rat model. The main results are as following:1 Effect of TFA on PSD rat modelMiddle cerebral artery occlusion(MCAO) 1 hour and reperfusion followed by isolation feed and irritable stimuli was used to induce PSD. The change of body weight,the crossing and rearing score in open-field test and sucrose drinking of PSD rat model were investigated regularly during the whole procedure. TFA (50,100mg/kg,qd×24d) could significant increase the body weight,the consumption of sucrose solution and the crossing and rearing score in open-field test in PSD rats. These findings indicate that TFA could effectively inhibit the depression behavior and show strong antidepressant effect.2 The antioxidation effect of TFA on PSD rat model UV spectrophotometer analysis technique was used to detect the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) in brain homogenate in PSD model rats. TFA(50,100mg/kg,qd×24d) can inhibit the increase of MDA content and increase the activities of GSH-Px in brain homogenate in PSD model rats, TFA(25,50,100mg/kg,qd×24d) could obviously enhance the activities of SOD.These evidences showed TFA have strong antioxidation effect and it may be another important mechanism of its antidepressant effect.3 The improvement of TFA on the indexes of hemorheology on PSD rat model The effects of TFA on the hemorrheology including whole blood viscosity, plasma viscosity,haematocrit (Hct) and erythrocyte deformation were observed.TFA (50,100mg/kg,qd×24d) could reduce the increase of whole blood viscosity at high-middle shear rates and increase the erythrocyte deformation. TFA (100mg/kg,qd×24d) could reduce the increase of whole blood viscosity at low shear rate and plasma viscosity. These results suggested TFA could effectively ameliorate the hemorheological indexes and it may also be another important mechanism of its antidepressant effect.4 The improvement of TFA on HPA axis on PSD rat model Radio-immunity analysis technique was used to detect the plasma levels of adrenocorticotropic hormone (ACTH) and cortisol in PSD model rats. The corticotropin releasing factor(CRF) protein expression was investigated by immunohistochemistry technique in the paraventricular nucleus (PVN) of hypothalamus.The CRFmRNA expression was semiquantified by reverse transcription-chain reaction(RT-PCR) in the hypothalamus. TFA(25,50,100mg/kg,qd×24d) could restore levels of ACTH and cortisol.TFA (50,100mg/kg,qd×24d) could significantly decrease the mean optical density values of CRF positive neurons,downregulate the excessive expression of CRFmRNA.These results suggested TFA could effectively inhibit hyperactivity of the HPA axis,this may be an important mechanism of its antidepressant effect.Conclusion:TFA exhibited antidepressant-like effect on PSD model rats,the mechanisms of it might be associated with its action on antioxidation,improvement on the indexes of hemorheology and inhibition effect on the activating of HPA axis.更多还原