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Experimental Research Of Pharmacodynamic Mechanism Of Nao Xin Tong Jiao Nang (NXTJN) In Treatment Of Ischemic Stroke

Posted on:2006-07-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Q LiuFull Text:PDF
GTID:1104360152488571Subject:Integrative basis
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Ischemic stroke, well known with its high incidence, high death rate, high relapse rate and high mutilation rate, is a life-theatening event in which part of the brain does not receive enough oxygen, usually due to a blood clot lodged in a cerebral artery. Stroke is a leading cause of death and disability in adults in developed and developing countries. Among the stroke patients who survive approximately half of them are expected to have lasting disabilities as a direct result of the event, requiring assistance in daily living. Ischemic stroke not only impaired patients` health, but also brought burden to the social. Therefore,it is an urgent task to further definite the pathophysiological mechanism of cerebral ischemia and to develop effective drugs of preventing and treating ischemic stroke. The pathophysiological mechanism of cerebral ischemia is very complex. Previous studies have demonstrated that it related with many factors, such as energy metabolism dysfunction of brain tissue following cerebral ischemic injury,inflammation damage, Glu injury, NO injury, massive free radicals injury, programmed cell death etc. At present the theory about cascade of damage have been raised, it included energy failure and excitotocity, peri-infarct depolarizations, inflammation and programmed cell death. Now the relations between cytokines, adhesion molecules and brain ischemia have been recognized. By now, there is lack of the novel therapeutic efficacy yet. On the contrary, therapeusis of Traditional Chinese Medicine (TCM) have special treatment preponderance. Nao Xin Tong Jiao Nang (NXTJN) is a capsule of compound prescription which has outstanding clinical effect. NXTJN on protecting cerebral ischemia injury were studied from different levels with the methods of biochemical assay, immunohistochemistry, enzyme-linked immunosorbent assay, molecular biology, cell culture, etc. So that it can provide the experiment proof for studying NXTJN pharmacodynamic mechanism of curing ischemic stroke. The main results were as follows: 1. The evaluation of model of middle cerebral artery occlusion (MCAO) in the rat by intraluminal suture The MCAO model is widely used for the cerebral ischemia in rats. The key to perform the model is to control the weight and age of the rats. Moreover, the family of the animal and the method of dealing with nylon suture can affect directly the success rate. Male Sprague-Dawley rats weighing 260-280g were anesthetized and subjected to 2 hours of temporary MCA occlusion by an intraluminal thread. The tip of the suture was blunted before it was used by heating it near a flame. In the studies in which a coated suture was used, a 20-mm distal segment of the suture was coated with poly-L-lysine(0.1%) and dried in a 60℃ oven for 1 hour. The diameter of the suture was 0.25 mm and not changed by the coating process. The suture was soaked in heparin(5 U/ml) before used. The suture was inserted 18 to 20 mm from the bifurcation of the common carotid artery (CCA), according to the animal's body weight. The animals were maintained at 36.5-37.5℃ with a heating pad during the operation. After the intraluminal suture was placed, the neck incision was closed with a silk suture. The animals were then awakened from anesthesia and returned to their cages. The model was valuated by behavioral testing, infarct assessment, water content and pathomorphology by histologic sections stained with hematoxylin and eosin (H E). Results shown that the modified suture model of MCAO was a usefull means of studying reversible facal cerebral ischemia. 2. Protective effect of NXTJN on ischemia-reperfusion injury in rat with MCAO After MCAO in rats, neurologic symptoms, brain infarction, cerebral edema and neuron damage occurred. The protective effects of NXTJN on rats subjected to MCAO were observed in the experiment. Results showed that NXTJN 0.24g/kg, 0.48g/kg can obviously attenuate the neurologic symptoms, reduced infarct size, decrease the water content of brain tissue and attenuate the neuron damage. 3. Inflammation mechanism...
Keywords/Search Tags:erebral ischemia, Cell adhesion molecule, Excitatory amino acid ( EAA ) Free radical, Nao Xin Tong Jiao Nang ( NXTJN ) Nitrogen monoxide ( NO ), rat cerebral microvascular endothelial cell ( rCMEC )
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