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The Expression Of HIF-1α In Intracerebral Hemorrhage And Its Significance

Posted on:2006-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:A Y WangFull Text:PDF
GTID:2144360155469759Subject:Neurology
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Intracereral hemorrhage(ICH) is one of the most popular diseases and the ICH induced by hypertension often results in higher mortality and morbidity among stroke patients. During the past several decades, many researchers have studied the pathophysiological mechanism of ICH with the aim of finding methods for restoring neurological function. But, There are still many problems that we can not understand. The studies have demonstrated that the cerebral edema is found after 6 hours of ICH in brain tissues around the intracerebral hematoma and aggrevated between 24 hours to 48 hours after ICH. Accordingly, Many neurons died lack of oxygen and blood gradually. But there are still a lot neurons survived from the hypoxia. We think the reason lies a new cytokine, hypoxia inducible factor-1(HIF-1),is engendered in ischemic brain tissues.HIF-1 a is a transcriptional activator, which adjusts the expression of a series of genes with the change of oxygen in cells and helps to sustain the hemotasis of oxygen. It is considered to play a key role in adaptation of neurons to hypoxia. Any decrease of concentration of oxygen can result in the appearance of HIF-1 quickly. HIF-1 is made up of two subunits, α subunit and β subunit. The studies have tested thatHIF-1 is relevant of surviving of neurons in low concentration of oxygen and is probably the direction of neuroprotction. In recent years, it is getting more and more attention to study ischemic cerebrovascular diseases. But there is not any experimental reports about expression of HIF-1 α in ICH in inland. In our studies ,we try to build up the model of cerebral hematoma to investigate the expression of HIF-1 α in ICH and try to find out its character, its correlation with the time and water content of ICH and significance. Materials and Methods:A total of 40 adult male-female Sprague-Dawley rats, weighing 250±30g, were used in this study. Animals were divided into 4 groups randomly, as follows: (1) control group n=10 (2)6h group after ICH, n=10 (3)24h group after ICH, n=10 (4) 72h group after ICH n=10. The blood from mice caudal vein was infused into the outside of right lateral capsule to build up the model of ICH. At the schedule time, the mice were anesthesia with an intraperitoneal injection of 30mg/kg sodium pentobarbital again. The brain was fixed by polyformaldehyde solution by left ventriculus sinister and taken out rapidly on ice. About 2×2×2mm3 brain tissue around hematoma was acquired to make HE tainting and SABC immunohistochemical method tainting. Furthermore, about 100 ± 20mg freshly dissected tissue samples from the side of hematoma were weighted immediately to determine the weight of the wet tissue, dried for 48 hours at 105℃ and re-weighted. The percentage of the water content was calculated as follows: %water=(wet weight-dry weight)/ wet weight ×100%The data were handled with SPSS 11.0 statistic software. The difference of groups were analyzed by t test and ANOVA; The difference of enumeration data were analyzed by Chi-square test; The correlation between HIF-1 α and water content was analyzed by Spearman correlation. Significant level is α =0.05. Results:1. HIF-1 α positive expression rates were 56.7%(17/30) in ICH brain tissues and 0 in normal brain tissues. The positive rate was significantly higher in ICH than in normal brain tissues (P<0.01). HIF-1 α positive expression rates were 30.0%(3/10) after 6 hours of ICH, 50.0%(5/10) after 24 hours of ICH and 90.0%(9/10) after 72 hours of ICH in pathology. HIF-1 α was highly expressed in brain tissue after ICH with the change of time (P<0.01).2.After intracerebral hemorrhage, the levels of cerebral water content raised gradually in different time , the means of water content is control group 77.53 ± 0.20%,6 hours group after ICH 78.59±0.41%,24 hours group after ICH 80.38 ± 0.52,72 hours group after ICH 80.79±0.75% and the levels of cerebral water content peaked at 72 hours in brain tissue(P<0.01).3. There were a positive correlation between HIF-1 α labeling index and the levels of water content(r=0.491, P<0.01). Conclusions:HIF-1 α is over expressed in ICH, and there is a significant correlation with the time and the levels of water content after ICH. It can probably help hypoxic neurons surviving in the condition of hypoxia.
Keywords/Search Tags:HIF-1α, intracerebral hemorrhage, immunohistochemistry, brain edema
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