氯胺酮对兔全脑缺血-再灌注海马细胞凋亡及TNF-β和IL-10的影响

摘要

目的 研究氯胺酮对兔全脑缺血-再灌注损伤中海马细胞凋亡及肿瘤坏死因子β(TNF-β)、白细胞介素-10(IL-10)表达的影响.方法 新西兰大白兔45只,随机分为三组,每组15只.A组仅分离股动脉、股静脉和双侧颈总动脉.B组和C组采用股动脉放血,夹毕颈总动脉30min制作全脑缺血-再灌注模型.C组经股静脉推注氯胺酮4.5 mg/kg.取海马组织行HE染色、TUNEL、免疫组化染色,计数CA1区存活细胞、凋亡细胞、TNF-β和IL-10阳性细胞个数.结果 再灌注后12～72 h,C组存活细胞明显多于B组(P＜0.05),凋亡细胞明显少于B组(P＜0.01).再灌注后6～72 h,B、C组TNF-β明显高于A组(P＜0.05).再灌注后6h和72 h,C组TNF-β明显少于B组(P＜0.05).再灌注后6h,C组IL-10阳性细胞数明显多于A、B型,再灌注后72 h明显少于A、B组(P＜0.05).结论 氯胺酮可通过调节细胞免疫应答,减轻炎症反应,减少细胞坏死和凋亡,具有良好的脑保护作用.%Objective To explore the effect of ketamine on apoptosis and the expression of tumor necrosis factor (TNF)-p, interleukin(lL)-10 of hippocampal cells in global cerebral ischemic reperfusion injury rabbits. Methods Forty-five adult healthy New Zealand white rabbits were equally randomized into three groups (n-15) - sham operation group (group A) , model group (group B) and model + ketamine group (group C). The model of global cerebral ischemia-reperfusion was produced by femoral arterial bloodletting combined common carolid occlusion (30 mm). Ketamine 4. 5 mg/kg was injected through femoral vein after carolid occlusion in group C. The survived neurons in the CA1 region of the hippocampus were observed by HE staining, and apoptosis was detected by TUNEL method. The numbers of TNF-β and IL-10 positive neurons were detected by immunohistochemical stains. Results Compared with group B, the numher of survival cells increased significantly in group C after 12-72 h of reperfusion (P<0. 05); thc number of apoptosis cells decreased significantly in group C after 12-72 h of reperfusion (F<0. 01). The positive expressions of TNF-p were higher in group B and C than in group A after 6-72 h of repcrfusion(P<0. 05), while the positive expressions of TNF-p were lower in group C than in group B afler 6 h and 72 h of reperfusion(P<0. 05). After 6 h of reperfusion, the positive expressions of IL-10 were higher in group C than in group A and B(P< 0.05), while IL-10 were lower in group C after 72 h of reperfusion(P<0. O5). Conclusion Ketamine protects brain injury through reducing inflammatory responses and decreasing the necrosis and apoptosis afler global cerebral ischem ia-reperfusion in rabbits