The Investigation Of The Effect Of Endotoxin And Tumor Necrosis Factor-α In Cerebral Hemorrhage In Rats Complicated By Multiple Organ Dysfunction Syndrome

Objective To establish a model of cerebral hemorrhage in rats complicated by multiple organ dysfunction syndrome (MODS); to investigate changes in tissue pathology of brain\lung\liver\intestines and kidney; to investigate plasma endotoxin and tumor necrosis factor- α gene expression in vital organs after cerebral hemorrhage ; To discuss the pathogenesis of cerebral hemorrhage complicated by MODS. Methods1. Cerebral hemorrhage was induced in rats by injecting different dose collagenase into the caudate nuclear. 96 Wister rats were randomly divided into 7 groups: normal control group (n=6), sham-operative group (n=6) and 2 groups of Cerebral hemorrhage(0.4U,0.8U)(n=42)including 4h, 8h, 12h, 24h, 36h, 48h, 72h seven time points.2. Changes of symptoms and signs including temperature , heart rate and respiration of each group were recorded, the amount of WBC and function of liver and kidney were assayed. Pathological changes of brain\lung\liver\intestmes and kidney were recorded and pictures were taken through optical microscope.3. The dose of plasma endotoxin were examined.4. The area density and optical density of positive staining expressing tumor necrosis factor- α mRNA were analyzed for the relative content of tumor necrosis factor- α using in situ hybridization and CMIA medical imaging analysis system.5. Results were expressed as X±S. One-way-ANOVA of SPSS 10.0 soft ware was used to evaluate the difference among groups. Correlation analysis of SPSS 10.0 was used, too. Results1. Hematoma was found 4h after collagenase injection in hemorrhage group and the hematoma would not enlarge after 24h. The hematom of group2 was larger than that of group 1 and the hematoma formed was stable. The neurological score of group 2 was much higher than that of group l(P<0.01).2. The rats of experimental group 1 and group 1 had higher temperature and respiration, and the levels of ALT, AST> BUN, Cts CK and LDH in those group improved. There were significant differences between operative group and normal control group, between operative group and sham-operative group, between group 1 and group 2. Incidences of systemic inflammatory response syndrome (SIRS) and MODS were respectively 75.4% and 21.4% after cerebral hemorrhage of groupl, Whereas incidences of SIRS and MODS were respectively 100% and 67.9% aftercerebral hemorrhage of group2.3. There was endotoxemia administration after acute cerebral hemorrhage. Plasma endotoxin level of experimental group 2 is higher than that of experimental group l(.P<0.01). Plasma endotoxin level started to increase at 8 hours after hemorrhage, peaking at 24 hours, then returned to the baseline value at 72 hours in experimental group 1, but it still maintain high level in experimental group 2.4. In experimental group there are various inflammatory lesions on the organ tissue at every time point , in experimental group 1 the organ has significantly pathological changes at 24-36 hour point, the changes gradually extinct in 48 hours, and it almost recovers normal at 72 hour point; in experimental group 2 the inflammatory reaction on lung and small intestine can be seen 4 hours after bleeding, after 12 hours nonspecific inflammatory reaction can be seen on lung\ intestinesMiver and kidney, the pathological changes become significant at 24-48 hour point, and there are still significantly inflammatory reaction at 72 hour.5. In normal matched control group and sham-operative group there are no tumor necrosis factor- a mRNA expression in organ tissue , after 8 hours experimental group 1the tumor necrosis factor-a mRNA expression in liver increased, after 12 hours experimental group 1 start to express in lung and small intestine, after 36 hours expression began decrease; in experimental group 2 the tumor necrosis factor-a mRNA expression in various tissue increased quickly with the time passed, it culminate after 24 hours, and maintain high level after 72 hours..Conclusion1. An experimental animal model of MODS can be established successfully through cerebral hemorrhage was induced in rats by injecting 0.8u collagenase into the caudate nuclear.2. Cerebral hemorrhage can cause lung\liver\ intestines\ kidney irnflamming lesions. Pathological changes of intestinal mucosa and liver function can provideconditions for development of MODS after cerebral hemorrhage.3. Endotoxemia occurred after cerebral hemorrhage, and the expression of TNF-a increased, which implicate that endotoxemia ang TNF- a may be the important factors that prompt MODS after cerebral hemorrhage.