Experimental Study Of PAR-1, HIF-1a, MMP-9and TIMP-1in Intracerebral Hemorrhage In Human

Experimental study of PAR-1, HIF-1a, MMP-9and TIMP-1in intracerebral hemorrhage in humanObjective:In recent years, a large number of animal experiments or human peripheral blood studies showed that thrombin as neurotoxic substances plays an important role in the formation mechanism of the brain edema of hypertensive cerebral hemorrhage. Thrombin by P38MAPK pathway activated vascular smooth muscle cells of HIF-1, P38to regulate HIF-1over expression, and thrombin, and HIF-la activation by HIF-1phosphorylation and start another brain edema caused cause of the child of MMP-9expression, to participate in the formation of cerebral edema. According to the investigation, the rare human brain tissue PAR-1, HIF-la and MMP-9, TIMP-1in clinical research reports. Extravascular role of thrombin is achieved through the thrombin receptor PAR-1. Therefore, the study of human hypertensive cerebral hemorrhage at different time points after hemorrhage and brain tissue of PAR-1, HIF-la and MMP-9, TIMP-1. Clear specific pathways of the thrombin-mediated edema after intracerebral hemorrhage and the role of link. Validation PAR-1, HIF-la, MMP-9, TIMP-1in the back of the role of intracerebral hemorrhage edema, clearly people after intracerebral hemorrhage of thrombin mediated the specific route and edema action segment.Methods:From January2009to July2010in JiLin university for high blood pressure cerebral hemorrhage, the first hospital neurosurgery, could work clear hematoma surgical treatment patients24cases, the road will be within the scope of the hematoma channel next to the brain as the case group specimens, some patients cortex "colostomy " starting place namely hematoma parts over brain tissue, as the control group specimens, a total of6cases. According to the time of the case group is divided into<6h,6to24h,24h-3d,>3d group, using immunohistochemical method to detect24cases focal cerebral hemorrhage week6cases organization and normal brain tissue each time point PAR-1, HIF-la and MMP-9, TIMP-1expression, RT-PCR method to detect HIF-1a and MMP-9, TIMP-1expression, the Western blot test TIMP-1the protein expression, and through the dry wet weighing method combined with brain edema carries on the analysis, the electron microscope blood brain barrier dynamic change, discusses PAR-1,HIF-la and MMP-9,TIMP-1in the brain edema occurrence, development process in the possible role, and the correlation and clinical significance.Results:1. The water content of the brain changes, cerebral hemorrhage afterbrain edema degree with bleeding the extension of time progressive, in bleeding within6h water content, it started to increase,24h after a significantly higher,3d peak around, and then reduce (P<0.05). 2. ICH under electron microscopy after6h inside, less cytoplasm, cytoplasm ribosomes is more, organelles other less. Edema area nerve cells and stellate cell cytoplasm and the nucleus began swelling.6to24h damage increase, edema area nerve cells and stellate cell cytoplasm and nuclear mild swelling, neurons have less show dark cell samples change, still not obvious, the mitochondria swelling of the mild, crest a shorter or disappear, secondary lysosomes increase, ribosomes reduce, capillary surrounding astrocytes foot processes swelling, still and capillary basement membrane is linked together, endothelial cells mild swelling.24h-3d and brain swelling obviously increase, neurons and glia dissolution, mitochondria swell, deformation, solid shrinkage, crest a shorter or disappear, ribosomes reduce, the empty bubble cytoplasm, nuclear chromatin the edge set, organelles structure disorder is not clear, deep dye, BBB obvious damage. Capillary no significant change.3d, the cytoplasm mitochondria swelling of the mild, rough endoplasmic reticulum and ribosomes organelles such as the basic normal. Swelling of the brain is somewhat better, glial cells start to shrink.3. In one week in focal cerebral hemorrhage hematoma PAR-1, HIF-la, MMP-9, TIMP-1a rate of expression, the control group and bleeding group significantly by sexual meaning (P<0.05), and bleeding between groups are comparison of difference (P<0.05). Bleeding after6h immune cells began to increase the number of positive,24h-3d group is the maximum number of positive cells, and then gradually decreases. PAR-1, HIF-la, MMP-9, TIMP-1a positive correlation with cerebral edema.4. PAR-1and HIF-la protein expression are related (r=0.8809, P<0.05), PAR-1and MMP-9protein expression are related (r=0.9080, P<0.05), HIF-la and MMP-9protein expression are related (r=0.8632, P<0.05).Conclusion:1. Surrounding cerebral hemorrhage, the expression of PAR-1, HIF-la, MMP-9and TIMP-1increased significantly, and brain edema closely related.2. The abnormal expression of PAR-1, HIF-la and MMP-9, TIMP-1plays an important role in early brain edema.3. PAR-1, HIF-1a and MMP-9significantly related to collaborative or complementary approach to the common participation, promote the occurrence of cerebral edema.