| Objective: Traumatic brain injury(TBI) is a common factor resulted in disability and death of human being. Up to now, no ideal brain-protective agent has been found, so it is very important to serach for such an agent to reduce TBI. The process of brain damage not only occured at the time when a force acted on head, which was defined as primary brain injury; but also secondary brain injury would be occured during an interial time from several hours to days after accident, which is an important pathological process of traumatic encephalopathy and the site of action to realize protection of brain by using of medical measures. Recently, it was demonstrated that apoptosis participated in the pathogenesis of secondary brain damage after TBI. Most injured cells undergo necrosis in the central area of contusion. However, in the boundary of contusion, named"traumatic penumbra zone", the hurt is less severe and most injured cells undergo apoptosis. The traumatic penumbra may alter according to the changes of outside condition. When the condition is better, it can be reversed to the normal cell region(reversible); On the contrary, it will be exacerbated into a necrosis region(ire-versible), and neurological dysfunction will be aggravated. Apoptosis is a complex cascade of cellular suicide, and induced mainly by the activation of proteases of caspase family. Among this family, caspase-3 is a key enzyme in mammalian cell apoptosis, which initiates the executive phase of apoptosis. The aim of the present study is to investigate neuroprotective effect of simvastatin on traumatic brain injury in rats by observing apoptosis of brain cells, expression of caspase-3 and water containing of edema brain in TBI rats.Methods: 36 healthy male SD rats were randomly divided into three groups (n=12).①Simvastatin Group: Rats were contused on brain by fluid percussion. Those animals were orally administrated with Simvastatin (20mg/kgwt) dissolved by 2ml Normal Saline (NS) when they came round, and then once daily.②Normal Saline Group: Animal models were given with equal NS instead of Simvastatin.③Shamed-operation Group: Burr hole on the skull was only finished for rats treated as those in Normal Saline group. The rat's brain was removed under anaesthesia at 72 hour after injury. (200±50)mg brain tissue on anterior of"penumbra zone"around contusion zone was obtained for measure brain water content; The posterior of'penumbra zone'and hippocampus for observation on expression of caspase-3 by immunohistochemistry and apoptosis by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Results:1. The effect of simvastatin on brain water content in"traumatic penumbra zone"of rats at 72h after contusion: The brain water content in'penumbra zone'of Simvastatin Group, Normal Saline Group and Shamed-operation Group respectively is (79.72±1.81)%,(86.21±1.44)% and (73.66±1.2)%; The water content of injuried side in the Simvastatin Group and Normal Saline Group were increased obviously than that in the Shamed-operation Group(P<0.05). But the water content of the injured side in the Simvastatin Group reduced obviously(P<0.05) than that in Normal Saline Group.2. TUNEL Staining: there are few TUNEL-positive neurons in Shamed-operation animals. After TBI, the TUNEL-positive neuronal cells increased significantly in'penumbra zone'and hippocampus, apoptotic index respectively is (22.72±4.0)%,(11.80±1.47)%, accordingly in Shamed-operation respectively is (0.87±0.17)%,(0.2±0.08)%. (P<0.05, compared with Shamed-operation group). Simvastatin Group sharply decreased the number of TUNEL-positive neuronal cells induced by TBI accordingly index respectively is (18.29±2.38)%,(7.07±1.04)% (P<0.05, compared with Normal Saline Group), which is, however, more than that of Shamed-operation group(P<0.05).3. Expression of caspase-3: Caspase-3 expression in cerebrum increased significantly after TBI, especially in the areas surrounding the injured lesions and hippocampus. The results of the Caspase-3 positive cells in penumbra zone and hippocampus respectively are 17.91±2.01,8.61±1.70 in Simvastatin Group. Accordingly results in Normal Saline Group are 23.85±3.40,12.89±1.96. Simvastatin inhibited the expression of caspase-3 induced by TBI(P<0.05, compared with Normal Saline Group). But more than that of Shamed-operation group(P<0.05).Conclusions: Simvastatin lighten edema significantly in'penumbra zone'around contusion in rats, and it has a pharmacodynamic action to restrain the apoptosis in'penumbra zone'and hippocampus. its molecular mechanism might be related to the activation of inhibit expression of caspase-3. |
PDF Full Text Request