Experimental Studies Of Brain-Gaster Syndrome Induced By Intracerebral Hemorrhage

Part 1: The experimental study of the expression of MMP-9 in tissue around experimental cerebral hemorrhagic focus and their relations with brain injury and brain edema【Preface】:There are inflammatory reactions and edema in the brain tissue around the experimental cerebral hemorrhagic focus. The inflammatory reactions are related to brain cell injury,neuronal apoptosis, and cellular necrosis. The inflammatory reactions are related to brain edema. The inflammatory and edema in tissue around cerebral hemorrhagic focus influence the patient's condition and results. The prerequisite of inflammation of brain tissue around cerebral hemorrhagic focus due to inflammatory cells breakthrough the Blood-brain barrier, then get into the brain. This great process that inflammatory cells breakthrough the Blood-brain barrier and get into the brain is provoked by matrix metalloproteinases-9.【Objective】To explore the dynamic changes of MMP-9 in tissue around hemorrhagic focus, and to analyze the relation with the changes, brain edema, neuronal apoptosis and brain injury. To illuminate the functions of MMP-9 in tissue around the cerebral hemorrhagic focus. Then to find a new approach which suit to the cure of cerebral hemorrhage.【Methods】ICH model was produced by infusing autologous fresh blood taken from rat caudal artery into the right caudate nucleus to simulate the natural condition of ICH. The sixty-four SD rats were randomly divided into three groups: control group, sham experimental ICH group and operation ICH groups. In operation group six time points of 12h, 24h, 48h, 72h, 96h and 120h after ICH were chosen, and eight rats for each time point. The expression of MMP-9 was detected by using immunohistochemical method and RT-PCR. The apoptotic ceils were examined through the methods of TUNEL Brain water content (BWC) was determined by comparison of wet and dry weight. Pathological changes were observed with transmission electron microscope. The neurobehavioral function was evaluated through the methods of Longa, Berderson and balancing beam. 【Results】Dynamic observation was made at different time points after ICH. 1. The expression of cerebral water content in the hemorrhage site began to increase after 12 hours (P<0.01), and reached maximum levels by 72 hours (P<0.01), then decreased to normal level by 120 hours. 2. The expression of MMP-9 began to increase after 12 hours (P<0.01) and reached the peek after 48 hours (P<0.0l). MMP-9 expressed still potently after 120 hours (P<0.0l). There was a positive association between MMP-9 and the cerebral water content at time points from 12 hours to 120 hours(r=0.914, P<0.05). There was also a positive association between MMP-9 and the cerebral water content at time points from 12 hours to 120 hours(r=0.829, P<0.05). No obvious changes of MMP-9 and neuronal apoptosis were observed in control group almost.【Conclusions】These results suggested that the expression of MMP-9 increased at different time points from 12 hours to 72 hours after ICH, and were positively correlated with the increase of cerebral water content and neuronal apoptosis. MMP-9 may contribute to the brain edema and neuronal apoptosis.Part 2: The experimental study of acute gastric mucosal lesion induced by intracerebral hemorrhage【Preface】:Intracerebral hemorrhage (ICH) is a common clinical disease with high morbidity and mortality. The acute gastric mucosal lesion is a common complication of intracerebral hemorrhage and its clinical situations are hyperemia in gastric mucosa, erosion and ulcer. So it influence patient's prognosis. The development is due to many factors, such as reducing factors related to gastric defense and enhancing gastric aggressive factors. Prostaglandin E2 is crucial for the maintenance of the gastric integrity, which produce a significant rise in the GBF, facilitate gastric mucosal lesion and so on. That many drugs and factors accommodate the expression of prostaglandin E2 effect the reparation of gastric mucosal lesion.【Objective】To observe the changes of PH in gastric juice, blood flow and Prostaglandin E2 in gastric mucosa after intracerebral hemorrhage, as well as to explore the correlation between the changes and gastric mucosal lesion. Then reveal the contribution of Prostaglandin E2 in gastric mucosa after intracerebral hemorrhage.【Methods】ICH model was produced by infusing autologous fresh blood taken from rat caudal artery into the right caudate nucleus to simulate the natural condition of ICH. The xixty-four SD rats were randomly divided into three groups: control group, sham experimental ICH group and operation ICH groups. In operation group six time points of 12h, 24h, 48h, 72h, 96h and 120h after ICH were chosen, and eight rats for each time point. PGE2 examined by radioimmunoassay. PH in gastric juice, the ulcer index score, gastric mucosal blood flow in the mucosa were also detected.【Results】Dynamic observation was made at different time points after ICH.1. The PH in gastric juice began to decrease after 12 hours (P<0.05), and reached minimum levels by 24 hours (P<0.01), then increased to normal level by 120 hours. 2. The gastric blood flow began to decrease after 12 hours (P<0.0l) and reached the minimum after 96 hours (P<0.01).3. The expression of PGE2 began to decrease after 12 hours (P<0.0l) and reached the minimum after 96 hours (P<0.01).4. The ulcer index decreased after ICH (P<0.0l). 5. There was a positive association between PGE2 and GMBF at time points from 12 hours to 120 hours(r=0.977, P=0.004). There was a negative association between PGE2 and ulcer index from 12h to 120h(r=-0.963, P=0.008). There was also a negative association between GMBF and ulcer index at time points from 12 hours to 120 hours(r=-0.966, P=0.007).【Conclusions】These results suggested that the acute gastric mucosal lesion was induced by intracerebral hemorrhage. There were associations with acute gastric mucosal lesion and PGE2 in gastric mucosa,GMBF,PH in gastric juice,ulcer index.