| Objective:Established by injection of the caudate nucleus of rat tails blood autologous blood injection model of cerebral hemorrhage, and give to edaravone injection therapy, the effects of different doses of edaravone in rats after intracerebral hemorrhage and neurological function brain tissue of Caspase-3(cysteinyl aspartate-specific proteinase-3)and PARP-1[poly(ADP-ribose)-polymerase- 1],affect the expression of apoptosis for the treatment of cerebral hemorrhage edaravone provide experimental evidence. Methods:The weight in a healthy adult male between 250g-300 g 80 SD rats were randomly divided into sham group(5), ICH group(25), low-dose group, hereinafter referred to as low-dose treatment group(25) and high-dose treatment group hereinafter referred to as high-dose group(25) into four groups.Sham-operated rats in which the modeling process, only the pins but not autologous blood injection, set up only after 6h time point; ICH group, low dose group and high-dose treatment groups each were taken five time points, respectively, after 6h, 24 h, 2d, 3d, 5d rats were sacrificed at each time point five rats. Experiments using rat tails blood autologous blood injection into the right caudate nucleus of rat brain hemorrhage model Methods. Low-dose treatment group were accordingto the weight 1mg / Kg, high-dose treatment groups according to body weight after 3mg / Kg(diluted with saline to 2 ml) to give edaravone intraperitoneally injected once every 12 h until 12 h before death. ICH rats at different times after injection of the same dose administered saline, sham group except without the injection of autologous blood, the rest of the group is consistent with ICH. 2h determine whether cerebral hemorrhage after a successful model and five time points after surgery neurological score. The rats were killed after a time point immediately craniotomy brain tissue, brain water content was measured(wet weight method) were intracerebral hemorrhage in tissues, Caspase-3 and PARP-1 positive cells(immunohistochemistry staining), apoptotic cells(TUNEL staining) and pathological staining(HE staining). Results:1. Intracerebral hemorrhage after surgery, 6h after ICH rats began to appear in varying degrees of neurological disorders, brain hemorrhage surrounding water increases, and both peaked in 2-3d, The number of apoptotic cells also increased, the number of apoptotic cells in the 3D of the most, HE staining display ipsilateral cerebral hemorrhage after brain hemorrhage performance.2.Cerebral hemorrhage Caspase-3, PARP-1 dynamics: 6h Caspase-3 expression increased cerebral hemorrhage after surgery compared with the sham group, there were significant differences(P <0.05), 3d after the peak, then gradually decreased, the first 5d still high expression, the expression of PARP-1 todisplay the same rule. 3. Edaravone impact on these indicators:(1)cerebral hemorrhage after surgery, the two treatment groups of rats neurological function compared with ICH group were significantly higher scores, low-dose treatment group that is statistically significant(P <0.05) and at 24 h after ICH group, large dose treatment group after 6h and ICH group had statistically significant(P <0.05), to the two treatment groups after 5d and ICH group were statistically significant(P <0.05), at each time point after 6h after high dose treatment group and low dosetreatment group comparison of Caspase-3 and PARP-1 expression decreased,there was significant difference(P<0.05);(2) high and low dose group postoperative hematoma surrounding brain tissue water content at various time points with ICH group has been reduced significantly different(P <0.05), high-dose treatment group reduced brain water content at different time points after treatment with low-dose group, a significant difference(P <0.05);(3) HE staining of high and low dose group hemorrhagic necrosis of nerve cells surrounding brain tissue, cell edema and leukocyte infiltration ICH group at all time points compared to alleviate, high-dose treatment groups of brain tissue pathological change mitigation at different time points after treatment with low-dose group;(4) after cerebral hemorrhage, high and low dose group PERIHEMATOMA in Caspase-3 and PARP-1 expression at each time point was significantly lower than the ICH, there are significant differences(P <0.05), high-dosetreatment group at all time points after treatment with low-dose group Caspase-3 and PARP-1 expression decreased, there are significant differences(P <0.05);(5) high and low dose group PERIHEMATOMA in the number of apoptotic cells at each time point was significantly lower than the ICH, there are significant differences(P <0.05), high-dose treatment group were relatively lower number of apoptotic cells at different time points after treatment with low-dose group, a significant difference(P <0.05). Conclusion:1. Take autologous blood injection rat model of intracerebral hemorrhage is simple, high success rate, easy to operate, but also with the pathophysiology of human spontaneous intracerebral hemorrhage on the clinical course similar to an ideal cerebral hemorrhage animal models. 2. After intracerebral hemorrhage increased expression of Caspase-3 and promotes expression of PARP-1 protein, will increase cerebral edema and pathological changes in the brain, leading to neurological function, promotes apoptosis, thereby increasing bleeding after secondary brain Injury. 3. Immediately after intracerebral hemorrhage given edaravone treatment can inhibit the expression of Caspase-3 and PARP-1, reduces neuronal apoptosis after intracerebral hemorrhage, cerebral edema, brain tissue and the degree of pathological changes, improve neurological function, to continue onset of brain injury to play a protective role. 4.The neuroprotective effects of edaravone in the treatment of cerebral hemorrhage increases with thedose, high-dose effects of edaravone than low doses. |
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