Active Ingredient Of Anemarrhena Protective Effect On Cerebral Ischemia And Its Mechanism Research

Stroke, especially ischemic stroke, is a common disease which is threatening the health ofpeople. The disease not only impaired patients' health, but also brings burden to the social.Therefore,it is an urgent task to further definite the pathophysiological mechanism of cerebralischemia and to develop effective drugs of preventing and treating ischemic stroke. The pathophysiological mechanism of cerebral ischemia is very complex. Previous studieshave demonstrated that it related with many factors, such as energy metabolism dysfunction ofbrain tissue following cerebral ischemic injury , massive free radicals producing, [Ca2+]irising,platelet activation, changes of hemorheology, inflammation damage, etc. At present thetheory about cascade of damage have been raised, it included energy failure and excitotocity,peri-infarct depolarizations, inflammation and programmed cell death. Now the relationsbetween cytokines,adhesion molecules, NF-κB and brain ischemia have been recognized. Effective component in Zhimu(Compound 9714)was a soluble steroidal saponin which wasextracted from Chinese medcine Zhimu.In this paper,the effects and mechanisms of Compound9714 on protecting cerebral ischemia were studied from different levels with the methods ofbiochemical assay, immunohistochemistry, enzyme-linked immunosorbent assay, molecularbiology, cell culture, etc. So that it can provide the theory and experiment proof for studying newmedicine of curing brain ischemia. The main results were as follows:1 Improvement effect of compound 9714 on brain function deterioration of animals The descent of learning and memory ability was a typical display of brain disfunctioninduced by ischemia. Morris water maze was used to measure the effect of compound 9714 onlearning and memory ability of brain ischemia rats induced by common carotid arteryocc1usion(CCAO), HE and SABC immunohistochemistry staining were used to study itsmechanism. Mice water maze was used to measure learning and memory ability of mice inducedby scopolamine. Western Blottin was used to measure the effect of compound 9714 onCholinergic receptor. Results showed that compound 9714 10, 20, 40mg/kg can shorten theescape latency time and increase the percent of primary flat floor quadrant swimming distance ofmodle rats in Morris water maze.Compound 9714 can improve the degeneration and necrosis ofneuron in HE staining.Compound 9714 20mg/kg, 40mg/kg can improve the expression of BDNFand decresed the expression of ICAM-1. Compound 9714 15mg/kg, 30mg/kg, 60mg/kg canimprove the learning and memory ability of acquired memory disturbance mice induced byscopolamine. Compound 9714 15mg/kg, 60mg/kg can inhance the cholinergic receptor(M1,Nalpha7) density of acquired memory disturbance mice induced by Scopolamine.英文摘要 52 Protective effect of compound 9714 on ischemia injury rats Brain ischemia model included focal brain ischemia and whole brain ischemia. Middlecerebral artery thrombus(MCAT) model induced by FeCl3 and middle cerebral arteryocclusion(MCAO) model induced by inserting a monofilament suture were used to study theeffect of Compound 9714 on ischemia injury rats. Results showed that Compound 9714 20,40mg/kg can obviously reduce infarct size, attenuate the neurologic symptoms, decrease thewater content of brain tissue. Compound 9714 10, 20, 40mg/kg can also improve brain bloodflow of model rats, can inhance the activity of T-SOD, decrease the activity of MPO, T-NOS, i-NOS, decrease the content of NO and MDA in brain tissue of MCAO model rats.3 The influence of compound 9714 on thrombosis, platelet aggregation and hemorheology Thrombosis formation was an important course in brain ischemia, it related to vessel, bloodcomponent and blood flow. After cerebral ischemia, platelet aggregated and blood component,hemorheology changed. Platelet aggregation was the initiation factor of thrombosi...