| Background and Objective: Intracerebral Hemorrhage (ICH) is a severe cerebrovascular diseases, belonging to the category of stroke in Traditional Chinese Medicine (TCM). Since the view of Qixu Xueyu was proposed by a famous doctor in Qing dynasty, named Wang Qingren, who initiated the prescription of Buyang Huanwu Decoction, Yiqi Huoxue (YQHX) therapy has been widely used in clinic. Modern researches have proved YQHX therapy can improve the circulation in the brain, rectify the blood rheology change and promote the recovery of the nervous system, etc. The microvessel system of the hematoma zone may be destroyed after ICH. The improvement of nervous function depends on the reestablishment of cerebral blood flow, so the reconstruction of microvessel system through angiogenesis is one of important processes of the brain tissue repair. The priming of angiogenesis needs the basal membrane of capillary endothelial cell and extracellular matrix degradation, which demands the participation of matrixmetalloproteinases, Most previous researches of MMPs were concentrated on destroying blood-brain barrier(BBB), vasogenic brain edema and angiogenesis in tumor aversion, but MMPs may play important roles during the repair phases of stroke, particularly during angiogenesis and reestablishment of cerebral blood flow. Therefore, we presume that YQHX therapy may be good to reconstruction of the microvessel, improving the microenvironment and promoting the recovery ofneurofunction through regulating expression of MT1-MMP, MMP-2 MM-9. The objective of this experiment is to investigate the effectof YQHX therapy on expression of MT1-MMP,MMP-2 and MMP-9 in the microvessel endothelial cells, and to probe the mech-anism of YQHX therapy doing to the restructing of microvessel vessel system in the hematoma zone after ICH.Methods: 155 SD rats were randomly divided into six groups including normal control group, sham control group, model control group, sham control group, YQ therapy group, HX therapy group and YQHX therapy group. By injecting collagenase typeⅦstereotaxically into right globus, ICH model was made. YQHX group therapy, YQ therapy group, HX therapy group and were respectively administered at Buyang Huanwu decoction(30.80g/kg.d), YiQi decoction(16.20g/kg.d),HuoXue decoction(14.60g/kg.d). Every rat was caculated on forelimb use asymmetry before it was executed; At 2d, 4d, 7d, 14d, 21d and 28d after administered, rats were randomly chosen to be perfused transcardically. Immunohistochemistry was used to examine the ruleon the expression of MT1-MMP, MMP-2 And MMP-9 in vascular endothelial cell nearby the haematoma, and observeing the effect of YQHX therapy.Results:1. The ratio of forelimb use asymmetry in ICH rats: Hemiparalysis symptoms were seen after ICH rapidly. At 4d, the ratio of forelimb use asymmetery descended notably (p＜0.05), but was higher than that sham control group. At 7d, the ratio in YQHX group rats became to be lower than that in model group rats. So these information hinted that YQHX therapy can decreased the ratio of forelimb use asymmetry of the rats with ICH.2. The morphology of MT1-MMP,MMP-2 and MMP-9 in ratbrains: Expression of MMP-2 was not observed in normal control group and was observed in the cortex of sham group occasionally. The difference of the morphology and distribution range was not obviously between the model group and the therapy-treated groups. Expression of MMPs mainly located on cerebral endothelial cells,macrophage and glia cell, where the brown infiltrated-form deposition could be seen in cell membrane and endochylema or ECM. In early period (2-4d), MMPs expressed extensively in the surrounding tissue of hematoma, as well as were observed in the opposite side cortex. After 7d, they were mainly observed in the surrounding tissue of hematoma and were not be seen in 3. The expressions of MT1-MMP,MMP-2 and MMP-9 in microvessel endothelial cells of ICH rat brains: The expressions of three indexes were not obviously difference between every ICH groups at 2d; In model group, the expression ofMT1-MMP, MMP-2 peaked at 4d (p＜0.01), then gradually decreased but peaked at 14-21d again (p＜0.01). In YQHX-treated group, the expression of MT1-MMP,MMP-2 were lowest than that in model group and other therapy-treated groups at 4d (p＜0.05). In YQHX-treated group, the expression of MT1-MMP peaked at 7-14d, which more early than that in model group. In every therapy-treated groups, the expression of MT1-MMP is obviouslylower than that in model group after 21d (p＜0.01). In YQHX treated group, the expression of MMP-2 has been present a high level after 7d, which was higher than those in the other groups (p＜0.05) at 7～28d, then depressed at 28d. In model group, the expression of MMP-9 peaked at 4d (p＜0.01) and decreased gradually, then could not be observed after two weeks, but in YQHX-treated group, the expression of MMP-9 peaked at 7d (p＜0.01) which was delayed than that in model group (p＜0.05), then depressed gradually, and could not be observed at 28d.Conclusions: the expressions of MT1-MMP,MMP-2and MMP-9 in vascular vessel endothelia cells of rat brains were increased after ICH, the expression of MMP-9 was obviously in the early ICH period; The expression level of MT1-MMP, MMP-2 were still high in injury midanaphase. They may participate in angiogenesis in reparative process after ICH. YQHX Therapy could regulate the expressions of MT 1-MMP,MMP-2 And MMP-9 in ICH rat brains, which may improve the niche and promote the microvessel networks reconstruction following ICH. |
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