| 1 BackgroundPure cerebral ischemia in clinical morbidity is low, which caused embolism only in the mural thrombus atrialfibrillation off, infectious pus bolt, cancer cells embolus, parasitic ovum embolus and so on. Most cerebral ischemia is occurred in some basis pathological changes under conditions, such as high blood pressure, hyperlipidemia and diabetes. These basic lesions are ischemic stroke risk factors, which have some effection or function. Although ischemic has the common physiological pathology changes process with brain edema, blood high condensation state, free radical damage, inflammation response, nerve cell necrosis and apoptosis, but there are some differences, and there are not exactly the same in ischemia degree, inflammatory response, the damage degree of neural function and the way of neuronal cell death. These differences may play an important role in the whole pathological process. And the same treatment is difficult to achieve satisfactory results. At present, few new drugs for treating stroke in market were researched for aiming to the basic pathological changes.Traditional Chinese medicine has a variety of understanding for ischemic stroke, the pathogenic mechanism mainly was involves in the "wind", "fire", "blood stasis", "phlegm" and "asthenia"; the pathogenic mechanism was different, a performance after stroke was also different; using the right recipe is treated with aiming to the different syndrome of TCM; Traditional Chinese medicine treats the dialectical stroke, which shows the advantages of Chinese medicine to treating complex diseases.This study was to putting traditional Chinese medicine theory and the mechanism of modern medical pathology and the pathophysiological theory system combined. Construct a compound model cerebral ischemia under the basic pathological changes conditions, relatively close to the actual situation of clinical, which provides to the standard model basis for determining the pharmacological mechanism of TCM and the curative effect.2 Objective1) Compare cerebral pathological differences between hyperlipidemia rat model and normal rat, and analyze the cerebral pathological character of hyperlipemia rat by studying inflammation and the influence on neurovascular unit in hyperlipidemia rat model.2) Study the character of hyperlipidemia concurrent cerebral ischemia and analyze the influence of hyperlipidemia inflammation factor on cerebral ischemia by comparing inflammation change in different time and neurovascular unit change between hyperlipidemia and cerebral ischemia model and normal rat.3 Method1) Building model:Building classic hyperlipidemia rat model with high fat diet, to confirm a successful model and detect the concent of serum lipid. Building middle cerebral artery occlusion model, and observe the brain ischemia injury of rat.2) Grouping:Dividing experimental rats into normal control, normal sham operation group,3 days,7 days after normal ischemia and hyperlipid, sham operation group,3 days,7 days after ischemia with hyperlipidemia, detect the behavior function score and cerebral infarction volume among different groups by behavior function scoring and TTC staining.3) Broken tail takes blood:Detect the content of ET-1, NO,6-keto-FGF1a, TX-B2, MCP-1, TNF-a, CRP, SOD, MDA and vWF in serum between groups by ELISA.4) Compare the difference expressions of MMP-2, (CAM-1, Bax, Bcl-2 and microvescular density (CD34) in rat brain by immunohistochemistry.5) Observe the pathological change in infarction zone among groups by H & E staining.6) Compare ultra structure change of cells around infarction by transmission electro microscopy technique.4 Results1) Compared to between hyperlipidemia group and normal group:①In hyperlipidemia group, NO and 6-keto-FGF1a is low in serum with significant difference (0.01<p<0.05), TX-B2 increased with significant difference (p<0.05); MCP-1, TNF-α, CRP, VWF, MDA significantly increased (p<0.01); MMP-2, ICAM-1 and CD34 increased in brain with significant difference (0.01<p<0.05).②Compared to normal group, in hyperlipidemia group, neuron withered slightly, mitochondria ridge shortened, rough endoplasmic reticulum reduced; capillary increased in cortex, mitochondria and mitochondria ridge increased in microvascular endothelial cell; glial cells and mitochondria ridge increased significantly; synapse and synaptic vesicle decreased, and mitochondria ridge shortened.2) Compared to between cerebral ischemia group and hyperlipidemia concurrent cerebral ischemia group:①Neuronal behavior function score has no significant difference on different time points. Nevertheless, there is significant difference between 3 days and 7 days after ischemia (p<0.05); D-value was minish with significant difference in 7 days, not in 3 days.②Infarction volume significantly shrinked in 7 days (p<0.05), not in 3 days (p>0.05).③NO,6-keto-FGF1a increased in cerebral ischemia model on 3 days and 7 days. There is significant difference between hyperlipemia and cerebral ischemia group and normal cerebral ischemia sham operation group (p<0.05); the content of NO and 6-keto-FGF1a in hyperlipemia and cerebral ischemia group compared to normal cerebral ischemia group were descreased, there is significant difference in 7 days (p<0.05), but not in 3 days after ischemia (p>0.05).④ET-1 showed high content trend at all time points of the cerebral ischemia model, but there is no significant difference in among groups and interclass (p>0.05). TX-B2 also showed high content trend at all time points of the cerebral ischemia model, which was increased with significant difference between hyperlipidemia and sham operation group (p<0.05), but no difference in hyperlipidemia concurrent cerebral ischemia and sham operation group (p>0.05). The expression of TX-B2 was decreased in cerebral ischemia compared to control, and there are significant difference between 3 days and 7 days after ischemia (p<0.05).⑤The content of vWF were increased at different time points of cerebral ischemia model. Compared to sham operation group, vWF was increased in 7 days after normal cerebral ischemia, with significant difference (p<0.05). Meanwhile, compared to sham operation group with hyperlipidemia, vWF was obviously increased in 3 days in hyperlipidemia concurrent cerebral ischemia group (p<0.05). Compared to normal cerebral ischemia group, in hyperlipidemia concurrent cerebral ischemia group, the content of vWF were higher with significant difference in 3 days and in 7 days after ischemia (p<0.05).⑥The content of MCP-1,TNF-αand CRP were increased in 3 days and 7 days after cerebral ischemia model. Compared to normal cerebral ischemia group, in hyperlipidemia concurrent cerebral ischemia group, the content of them were higher with significant difference in 3 days an d in 7 days after ischemia (p<0.05,0.01<p<0.05).⑦The expressions of MMP-2,ICAM-1,CD34 were increased in 3 days and 7 days after cerebral ischemia model. Compared to normal cerebral ischemia group, in hyperlipidemia concurrent cerebral ischemia group, the content of them were higher with significant difference in 3 days an d in 7 days after ischemia (p<0.05) ⑧Compared to normal sham operation group, the content of MDA was increased in 3 days after cerebral ischemia (p<0.05); compared to normal cerebral ischemia group, in hyperlipi demia concurrent cerebral ischemia group, MDA was obviously decreased in 3 days an d 7 days after ischemia (p<0.05); compared to cerebral ischemia group, the activity of SOD of the cerebral ischemia model were decreased with significant difference (p<0.05). The content of SOD was obviously decreased in the serum after cerebral ischemia in hyperlipidemia and normal groups, compared to sham operation groups and hyperlipidemia sham operation groups. SOD was obviously decreased in 3 days hyperlipidemia concurrent cerebral ischemia (p<0.05).⑨The expression of Bcl-2 and Bax were high in 3days and 7 days of cerebral ischemia models, compared to sham operation group, there were significant difference between hyperlipidemia concurrent cerebral ischemia group and cerebral ischemia group (p<0.05). Moreover, in hyperlipi demia concurrent cerebral ischemia group and cerebral ischemia group, the expressions of Bax in 3 days and 7 days after ischemia were evidently decreased (p<0.05), and Bcl-2 was increased in 3 days after cerebral ischemia. The ratio of Bcl-2/Bax was increased with significant difference in 3 days and 7 days after cerebral ischemia (p<0.05).⑩Histological observation of ischemia edge:Compared to normal cerebral ischemia, there were that extensive neuronal degenerated with necrosis, nuclear chromatin sparsed, crest cavity expansion; rough endoplasmic reticulum decreased significantly; small vascular endothelial cell swelled; cell junctions was disrupted; glial cell reaction hyperplasia was increased; the synaptic vesicles of synapses were re duced, meanwhile, the mitochon drial crest of cells of all became short or disappear, between crest cavity expan ding. This lesion was alleviate d in 7 days of ischemia, and compared to normal cerebral ischemia, the degeneration and necrosis and edema of neuronal was reduced, mitochon dria injury was restored, glial cells increased significantly, the mitochon drial cristae rich and endothelial cell edema decreased in hyperlipidemia concurrent cerebral ischemia group.5 Conclusion1) In the pathological process of hyperlipidemia, hyperlipidemia could damage of vascular endothelial cell and in duce d the inflammatory factors of brain, and effect on the the nerve-vascular unit.2) Inflammation and inflammatory related may be the pathogenesis biological basis of the phlegm and blood stasis.3) Under the condition of hyperlipidemia, the inflammatory factors has not only accumulated phenomenon, but also specific expression in the difference of cerebral ischemia period, which is contribute to the recovery of the lesion in recovery phase;4) For response to inflammatory stimuli in advance, the endogenous protected mechanism of brain was activated.
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