| Ischemic cerebrovascular disease is one of the important diseases that threaten the healthand life of humanbeings,and it also is the common disease in aged people,high in attact rate,death rate and mutilated rate. Base on the causes of this disease in Chinese Medicine as wind,fire, sputum or stagnation , and the determination of treatment based in pathogenesis obtainedthrough differentiation of symptoms and signs, we have gained some therapeutic effect.However, it is difficult to improve the therapeutic effect and clinical repeatability. For the pastfew years, along with the propose and advance of toxicant theory , and the deeper research ofits pathomechanism, it has formed a new viewpoint and focus on treating stroke throughcontrolling toxicant.Endogenous toxic materials is caused by disharmony of entrails , or dyscrasia of qi andblood, or wind, fire, sputum, stagnation and so on. All these endogenic pathogenic factorsinterties and interconvert and make organism disfouncsion and quality nature corruption, itaggravate the patient's condintion and so it is hard to interfere in. So, by the conduction ofendogenous toxic materials theory, we had a study on dynamic change of inflammatory factorsand their gene level on cerebral ischemia reperfusion rats to get the relationship betweenendogenous toxic materials and inflammatory factors so to understand how endogenous toxicmaterials generate and how they do harm to patients.Objective1. To observe the formation of endogenous toxic materials and its effective coursethrough observing dynamic change of inflammatory factors in focus cerebral ischemiareperfusion rats.2. To observe if the clearing brain and releasing orifices dripping pills with heat-clearingand detoxicating effect could lessen the acute cerebral ischemia damage through inhibiting theexpression of inflammatory factors.3. To explain the essence of endogenous toxic materials is to damage the brain tissuethrough explaining the poisoning effect of inflammatory factors and adhesion molecule to thenerve cell, and prove the effect is inreversible, It is the most important cause that stoke isdifficult to be cured. This provide a new theoretical support to the endogenous toxicant theoryof stroke, and endue"detoxication method"with a new biological connotation. in themeanwhile.Methods1. Suture-occuluded method was used to block the left middle cerebral artery to makeischemia for 1.5h, after reperfusion for 1h, 3h, 6h, 12h and 24h , the Zea longa method wasused to evaluate the neurologic impairment and immunohistochemistry method was used to detect the content of TNF-α, IL-1βin brain tissue, observe pathologic change in tissue at thesame time.2. After reperfusion for 12h, get the cerebral hemisphere which was made ischemia on iceplate after decapitation and prepare 10% tissue homogenate. ELISA method was used to detectthe content of TNF-α, IL-1 and ICAM-1.3. After reperfusion for 12h, get cortex issue and abstract the total RNA and detect theexpression of TNF-αmRNA and IL-1βmRNA.Results:1. Rats in model group appeared to be inactivity, fewer food-intake, poor spirit conditionand weight losing.2. Rats were lack of the symptom of neurologic impairment in sham operated group andshowed severe neurologic impairment in model group and, moreover, in treated group they gotmuch less neurologic impairment than model group.(P<0.05)3. Disorganization of structure layer of cerebral cortex is severe after reperfusion for 12h,pathological change in tussue showed that nerve cell swelling, and there was fragmentation,dissolve, pyknosis or disappear of cell nucleus which reach to top after reperfusion for 24h,while cortex structure of sham operated group was clear and those changes in treated groupwas much less..4. TNF-αin model group express after reperfusion for 3h, and reach to top after 24h,then decreased gradually. IL-1βin model group express after reperfusion for 6h, and reach totop after 12h, then decreased gradually. Both had statistical significance compared withsham operated group after reperfusion for 6h, 6h, 12h, 24h, 48h.5. After reperfusion for 12h, the content of TNF-α, IL-1β, ICAM-1 in model groupwere much higher than those in sham operated group(P<0.01).After treated with clearingbrain and releasing orifices dripping pills, all those factors decreased(P<0.05 or P<0.01)6. After reperfusion for 12h, the expression of TNF-α, IL-1βmRNA increased in modelgroup compared with sham operated group , and decreased in treated group.Conclusion1. After acute cerebral ischemia reperfusion, inflammatory factor such as TNF-α, IL-1βinmodel group obviously increased , showed a time-related change. Their peak value wasbetween 12h-24h, that proved they take part in the important course of cascade reaction ofcerebral ischemia reperfusion and was the cause of pathological lesion. Inflammatory factorssuch as TNF-αand IL-1βclosely related to the impairment of nerve cell, The dynamic changeand poisoning effect of them could explain the mechanism of formation of endogenous toxicmaterials and how they take effect.2. After reperfusion for 12h, TNF-α, IL-1β, ICAM-1mRNA and expression of theirproteinum increase in model group compared with sham operated group and decrease intreated group, that proved clearing brain and releasing orifices dripping pills with heat-clearingand detoxicating effect could lessen the acute cerebral ischemia damage through inhibiting the inflammatory reaction.3. The poisoning effect of inflammatory factors and adhesion molecule in course ofcascade reaction in acute ischemia is similar with the formation and effected course ofendogenous toxic materials in Chinese Medicine. These poisoning materials take the totaleffect and induce or aggrevate the cell necrosis or apoptosis and damage brain tissue in the end.That proved the essence of endogenous toxic materials is to damage the brain tissue,moreover , it is inreversible. This is the most important cause that stoke is difficult to be cured.4. The relation between inflammatory factors and adhesion molecule provide a newtheoretical support to the endogenous toxicant theory of stroke, and endue"detoxicationmethod"with a new biological connotation in the meanwhile.
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