摘要
BACKGROUND： Several studies have demonstrated that propofol exhibits protective effects in the central nervous system. OBJECTIVE： To observe the effects of propofol on neuronal apoptosis and aquaporin-4 （AQP-4） expression in a rat model of traumatic brain injury and to further investigate the mechanisms of action. DESIGN, TIME AND SETTING： The present neuronal, pathomorphological experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical College between April 2007 and March 2008. MATERIALS： Traumatic brain injury was induced by free falling objects in 150 healthy, male, Wistar rats. Propofol was produced by AstraZeneca, China. Rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemistry kit, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling （TUNEL） kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS： All 150 rats were randomly and evenly divided into lesion-only and propofol-treated groups. One hour after traumatic brain injury, propofol-treated animals received 1% propofol （10 mg/kg） through the caudal vein, followed by a sustained perfusion of 30 mg/kg propofol per hour for 2 hours, while the lesion-only group received equal volumes of physiological saline in parallel. MAIN OUTCOME MEASURES： At 6, 12, 24, 48, and 72 hours after traumatic brain injury, morphological changes in the peritraumatic and adjacent brain areas were analyzed in all rats by hematoxylin-eosin （HE） staining. In addition, cellular apoptosis was detected by TUNEL assay and the number of AQP-4-positive cells was determined by immunohistochemistry techniques. Brain water content was calculated as the ratio of dry to wet tissue weight. RESULTS： HE staining results demonstrated that, in the lesion-only group, the peritraumatic area exhibited neuronal and glial cell necrosis and disintegration. The adjacent area displayed swollen neuronal perikarya and vascular endothelial ceils, cellular edema, and a small amount of proliferating glial ceils. In contrast, these pathological changes were noticeably alleviated in the peritraumatic and adjacent areas of propofol-treated animals. Compared with the lesion-only group, the number of apoptotic cells was significantly decreased in the propofol-treated group at each time point after traumatic brain injury, in particular at 24 and 48 hours （P 〈 0.05-0.01）. In the lesion-only group, AQP-4 expression began to increase at 6 hours after traumatic brain injury, reached a peak level at 24-48 hours, and began to decrease by 72 hours. In the propofol-treated group, the number of AQP-4 positive cells was significantly less than the lesion-only group. This was the case at all time points, in particular at 12 and 24 hours （P 〈 0.01-0.05）. CONCLUSION： Propofol can dowuregulate neuronal apoptosis and AQP-4 expression in rats following traumatic brain injury, in particular at 24-48 hours.
BACKGROUND： Several studies have demonstrated that propofol exhibits protective effects in the central nervous system. OBJECTIVE： To observe the effects of propofol on neuronal apoptosis and aquaporin-4 （AQP-4） expression in a rat model of traumatic brain injury and to further investigate the mechanisms of action. DESIGN, TIME AND SETTING： The present neuronal, pathomorphological experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical College between April 2007 and March 2008. MATERIALS： Traumatic brain injury was induced by free falling objects in 150 healthy, male, Wistar rats. Propofol was produced by AstraZeneca, China. Rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemistry kit, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling （TUNEL） kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS： All 150 rats were randomly and evenly divided into lesion-only and propofol-treated groups. One hour after traumatic brain injury, propofol-treated animals received 1% propofol （10 mg/kg） through the caudal vein, followed by a sustained perfusion of 30 mg/kg propofol per hour for 2 hours, while the lesion-only group received equal volumes of physiological saline in parallel. MAIN OUTCOME MEASURES： At 6, 12, 24, 48, and 72 hours after traumatic brain injury, morphological changes in the peritraumatic and adjacent brain areas were analyzed in all rats by hematoxylin-eosin （HE） staining. In addition, cellular apoptosis was detected by TUNEL assay and the number of AQP-4-positive cells was determined by immunohistochemistry techniques. Brain water content was calculated as the ratio of dry to wet tissue weight. RESULTS： HE staining results demonstrated that, in the lesion-only group, the peritraumatic area exhibited neuronal and glial cell necrosis and disintegration. The adjacent area displayed swollen neuronal perikarya and vascular endothelial ceils, cellular edema, and a small amount of proliferating glial ceils. In contrast, these pathological changes were noticeably alleviated in the peritraumatic and adjacent areas of propofol-treated animals. Compared with the lesion-only group, the number of apoptotic cells was significantly decreased in the propofol-treated group at each time point after traumatic brain injury, in particular at 24 and 48 hours （P 〈 0.05-0.01）. In the lesion-only group, AQP-4 expression began to increase at 6 hours after traumatic brain injury, reached a peak level at 24-48 hours, and began to decrease by 72 hours. In the propofol-treated group, the number of AQP-4 positive cells was significantly less than the lesion-only group. This was the case at all time points, in particular at 12 and 24 hours （P 〈 0.01-0.05）. CONCLUSION： Propofol can dowuregulate neuronal apoptosis and AQP-4 expression in rats following traumatic brain injury, in particular at 24-48 hours.
