Effects Of Total Flavone Of A On Mice Model Of Post-stroke Depression And Its Mechanisms

Post-stroke depression (PSD)is a depression having a serious negative impact on rehabilitation following stroke. In rencent years,studies increasingly focus on Chinese- traditional medicine .Total flavones of abelmoschus manihot L(TFA) is the effective part,which was extracted from a chinese herb called abelmoschus manihot L.The constituents of TFA is identified by Hyperin,Quercetin and Isoquerctein .Our department former investigations indicated that TFA protected the neurons from the damage of cerebral ischemia .It hasn't been reported about the effect of TFA on PSD. Our research studied the effects of TFA on PSD and its possible mechanisms by using animal model.The main results are as follows:1 Effect of TFA on behavioral despair animal models in post-stroke miceMale mice were first subjected to repeated cerebral ischemia reperfusion, the forced swimming test and tail suspension test were given in post-stroke mice from 3,5,7and 5 days after surgery respectively.The result showed that TFA(160,80,40 mg·kg-1,ig,qd)could shorten the immobility time in forced swimming test of post-stroke mice on day5 postsurgery .On day5 postsurgery,TFA (160,80mg·kg-1ig,qd)shortened the immobility time in tail suspension of post-stroke mice. on day7 postsurgery, TFA(80mg·kg-1ig,qd)shortened the immobility time in forced swimming test of post-stroke mice. These evidences suggested that TFA could produce some protective effect in behavioral despair animal models in post-stroke mice. 2 Effect of TFA on chronic unpredictable stress model in post-stroke mice Setting up a mice model of PSD by using separated living and chronic unpredictable mild stress on the base model of Middle cerebral arrery occlusion 30min and reperfusion.mice were tested neurological function by neurologic deficit scores.We detected body weight and studied the behavioral determination by using method of calculation the preference of 1%sucrose,forced swimming test and step through test.TFA(160,80 mg·kg^-1,ig,qd×24d)could increase body weight . TFA(160,80,40 mg·kg^-1,ig,qd×24d)could promote neurological functional recovery.TFA(160,80,40 mg·kg^-1,ig,qd×24d)could increase the preference of 1%sucrose,decrease the duration of immobility in forced swimming test and improve the impairment of learning and memory. These evidences suggested that TFA could effectively inhibit the depression behavior and showed strong antidepressant effect on PSD model.3 The anti-lipid oxidatin effect of TFAUV spectrophotometer analysis technique was used to detect the MDA content and SOD,GSH-PX activity of brain homogenates.The result showed that TFA(160,80,40 mg·kg^-1,ig,qd×24d)could significantly inhibit the increase of MDA content and could obviously enhance the activities of SOD,GSH-PX in PSD mouse. These evidences showed TFA have strong anti-lipid oxidatin effect and this may also be another important mechanism of its effect on PSD .4 The improvement of TFA on abnormal hemorheologyThe test instrument of blood viscosity was used to detect the hemorheological changes.The result of hemorheological tests showed that TFA ( 160,80,40 mg·kg^-1,ig,qd×24d)could decrease the whole blood viscosity of PSD mouse. These evidences showed TFA have the effect on PSD,Which may be related to the improvement of abnormal hemorheology.5 Effect of TFA on hippocampus neuron injury in PSD miceHE staining,immunohistochemistry and Semi-quantitative RT-PCR technique were used to detect the histopathological changes,content of BDNF and analysis the expression of BDNFmRNA and CREBmRNA in PSD mice hippocampus .The result showed that TFA(160,80mg·kg^-1,ig,qd×24d)could obviously improve the histopathological changes and increase the content of BDNF,promote the expression of BDNFmRNA and CREBmRNA in PSD mice hippocampus. These results suggested TFA could effectively protect the hippocampus neuron injury, this may be an important mechanism of its effect on PSD.To sum up, our research indicated that TFA have distinctive antidepressant effect on behavioral despair animal models in post-stroke mice and mice model of post-stroke depression. The mechanisms of its effect on PSD might be associated with its action on anti-lipid oxidatin and the improvement on the activity of antioxidase and the abnormal hemorheology and the protection on the hippocampus neuron injury.