The Study Of The Protection Mechanism Of JNKSTâ…¢ On Cerebral Ischemia-reperfusion Injury In Rats

Background and aimIschemic cerebrovascular disease,as a common disease of people, with high possibilities of being attacked and disabled and high death and recurrence rates ,has done harm to human health. Now the application of the thrombolytic therapy in the initial stage is recognizede as the most ideal therapeutic tool now.But given the therapy,some patients'pathogenetic condition aggravated.It made the people question the safety of the thrombolytic,and play close attention to the cerebral ischemia-reperfusion injury.So,it becomes the hot point of the investigates that how to lessen the cerebral ischemia-reperfusion injury and more effectively improve the organism notor function of the patients who has the ischemic cerebrovascular disease.It was investigated that the injury induced by reperfusion after cerebral ischemia was correlated with several factors,such as the production of oxygen free radical,energy dysbolism,the toxic action of excitatory amino acids,the calcium overload,the change of gene expression and blood rheologthe.As the ischemic and hypoxia occurrences,the organism produces oxygen free radical in bulk.Oxygen free radical,a high activity matter,can react with the unsaturated fatty acids in the cell envelopes.It leads to the formation of the lipid peroxides, which can destroy the biomembrance.Eventually oxygen free radical can induce a a series of cascade reactions,which cause the neuronic injury and aggravate the functional disturbance of the organism.So the oxidative damage which was induced by oxygen free radical is the most important pathology link of the cerebral ischemia-reperfusion injury.Jiangniankangshuan tabletⅢ(JNKSTⅢ),a kind of traditional Chinese medicine,is established on the chief clinical therapeutic principle of nourishing qi and activating blood and on the years of clinical experience.The clinical evidence proved that JNKSTⅢshowed preventive effects on cerebrovascular disease by improving the blood rheology.And it can improve the patients'action disorder.It has no correlate research about the protect mechanism now. This experiment makes the cerebral ischemical reperfusion injury model by thread suppository.The purpose of this study is to investigate JNKSTⅢ's brain protection mechanism initially by antioxidative damage.So it can supply reliable experimental basis for the clinc more widespread application on cerebrovascular diseases of this medicine and the extenuation of the cerebral ischemia-reperfusion injury.Methods1. The establishment of animal model 96 healthy male SD rats,220～250g,were randomly divided into 6 groups,16 rats per group:control group, cerebral ischemia-reperfusion group(model),JNKSTⅢlow dosage group(JNKSTⅢl), JNKSTⅢmiddle dosage group(JNKSTⅢm), JNKSTⅢhigh dosage group(JNKSTⅢh) and nimodiping group(NIMO).Every drug was prepared suspl. according to the standard of 10ml/㎏ .JNKSTⅢgroups were administered by JNKSTⅢat dose of 0.36g,1.08g,3.24 g/(kg·d);NIMO group were given to NIMO 6mg/(kg·d).The model group was also given homo-volume aqua stillata once a day.After 7-days of intragastricd, the cerebral ischemical reperfusion injury models were made by string inserting method on the eight day.After the 2-hour's ischemia,the model group and every medication administration team were given 24-hour reperfusion.2. Every group rats were undertoken the evaluation of the neuroethology ,the blood rheology , the infarct volum partly.The ones were partly used to the study of the activity of lactate dehydrogenase (LDH),superoxide dismutase (SOD) and the content of malondial dehyde (MDA) in the blood serum and the brain tissue.The remaining ones were used to the expression of heat-shock protein 70 (HSP70) measured by immunohistochemistry.Results1. Neuroethology:Compared with the model group,every medication administration team could improve the neuroethology disord of the cerebral ischemia-reperfusion injury rats obviously ( p < 0.05 ) .Especially,the therapeutic effect of the JNKSTⅢh group and the NIMO group were more conspicuous.2. Blood rheology:The JNKSTⅢm group and the JNKSTⅢh group could depress the blood viscosity and the fibrinogen content,and raise the erythrocyte deformability.Compared with the model group,they were improved obviously(p<0.05或p<0.01).3. Infarct volum:The model group appeared evident cerebral infarction,every medication administration team can reduce the infarct volumes obviously(p<0.05).Especially,the effection of the JNKSTⅢh group and the NIMO group were more conspicuous.4. The determination of SOD,MDA and LDH in the blood serum and the brain tissue:After the cerebral ischemia-reperfusion, the activity of SOD depressed,and the content of MDA advanced in the blood serum and the brain tissue.The activity of LDH also steped up in the blood serum.The JNKSTⅢgroups could reverse the change,and the safety action depend on dose.5. The expression of HSP70 in the ischemic region brain tissue measured by immunohistochemistry:Compared with the model group,the expression of HSP70 in every medication administration team increased obviously(p<0.05).The expression in the JNKSTⅢh group and NIMO group raised conspicuously.Conclusion1. In the cerebral ischemia-reperfusion,JNKSTⅢcan improve the neuronethology symptoms by improving the blood rheology and the anti-oxidative injury.It also can reduce the infarct volumes.This is possibly one of the brain protection mechanisms of JNKSTⅢ.2. JNKSTⅢcan enhance the expression of HSP70 in the ischemic region of the brain tissue.It reduces the generation of the oxygen free radical,and evaluates the anti-oxidative capability of the cells.It maybe one of the important ring-joints of JNKSTⅢ's antioxidative injury mechanism.