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Against Cerebral Ischemia, And Mechanisms Of Ginkgolide B

Posted on:2006-07-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Y HuangFull Text:PDF
GTID:1114360152488565Subject:Integrative basis
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Cerebrovascullar disease,well known as its high incidence,high death rate,high relapse,and high multilation rate,is one of the most serious threat of human being.According to the epidemiological study,incidence of cerebrovascular disease is about 140-200/100000 population,average death rate is 100/100000 population.As aging,cerebrovascullar disease,especially ischemic one is one of the diseases,which threats health,life,society and family,it caused global attention.In our country the death rate of cerebrovascular disease has become ahead of all the diseases since 1997.The incidence of ischemic cerebrovascular disease is higher than hemorrhagic cerebrovascular disease.The pathological and physiological mechanism in cerebral ischemia is complex,at present,it is considered to be related with energy metabolism failure,excitoxity,free radicals,Ca2+ overload, platelet activation,inflammation dama- ge,et al.So making clearance of its pathological and physiological mechanisms,developing newly typical,effective drug with little side effect to prevent and treat cerebral ischemic injury is an object to resolve. Ginkgo biloba,also named Baiguo,has the name of "a senior plant " and natural living fossil,and has a high drug value.Ginkgo biloba extract was generally applicated to treat disease from the respiratory system and cardiovascular system or other systems. Ginkgo biloba extract protected obviously nerve system in vitro and in vivo,and it attenuated neuron injury.Flavonoids and lactones were its main constituents,it was proved that ginkgo flavonoids was an antioxygen element,and lactones was a special antagonism to platelet activating factor.Presently Ginkgobalide A, Ginkgobalide B, Ginkgobalide C, Ginkgobalide M , Ginkgobalide J and bilobalide were isolated and determined, Ginkgobalide B was an antagonism to platelet activating factor. GB was provided by Development department of Chinese People Liberation Generanal Hospital 301 hospital,it was extracted with ring closure. The object was used different technical methods to study the protective effect of GB on cerebral ischemia-reperfusion jnjury and its possible mechanisms,which was based on the overview of studying cerebral ischemia. 1Protective effect of GB on cerebral injury in focal cerebral ischemic rats GB protected rats with MCAT due to FeCl3 lesion,attenuating their infarct volume,amelior- rating their pathological changes.The protective effect of GB on transition zone neuron,infarct zone neuron and conrol zone neuron was studied, infarct zone neuron necrosis and trauma was delayed,control zone neuron adaptability enhanced,GB protected neuron body and dendrite. Rats were operated by 3h ischemia and 21h reperfusion,and GB was given im at the moment of ischemia,after 21h reperfusion,effect of GB on neurological defects and infarct size were observed.Results implicated,because of cerebral ischemia-reperfusion,cerebral infarct appeared with hemiparalysis and limbs debilitation,GB 8mg/kg and 4mg/kg attenuated neurological defects,decreased infarct size,their inhibition rate were 10.48% and 11.40% respectively. At the same time,effects of GB SOD activity,MDA content,GSH content,GSH-PX activity,CAT activity,NO content,ATPase activity,LDH activity and LD content in brain homogenate were observed. Results showed cerebral ischemia-reperfusion resulted in decrease of SOD activity,MDA content increased,LDH was higher than sham,compared with sham,LD content in vehicle was higher.Given GB 8mg/kg,4 mg/kg to them,SOD activity in the rats brain homogenate increased. Given GB 8mg/kg,4mg/kg,2mg/kg to them,MDA content and LDH activity reduced. And given GB 8mg/kg,4mg/kg,2mg/kg,LDH content did not decrease.As for NO content,CAT activity,GSH content,GSH-PX activity and ATPase activity in cerebral homogenate,cerebral ischemia-reperfusion induced NO content to rise,given GB8 mg/kg,4mg/kg,2mg/kg to rats,NO content reduced remarkedly,their P value was P<0.01, P<0.05, P<0.05.Compared with vehicle,CAT activity of the rats given GB 8 mg/kg,4mg/kg,2mg/kg increased.Compared with vehicle,GS...
Keywords/Search Tags:Ca2+overload, GB, HO-1, HO-2, IP3R, JAK-STAT pathway, mGluR1 α, mGluR5c, erebrali schemia, excitotoxity, cella poptosis, oxygens tress
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