氯胺酮诱导的热休克蛋白70在不同鼠龄大鼠海马中的表达

目的　探讨氯胺酮导致神经损害的可能机制。方法　 35只成年大鼠分别给予生理盐水和氯胺酮2 0 .0、4 0 .0、6 0 .0、80 .0、1 0 0 .0、1 2 0 .0 mg/ kg腹腔内注射 ;另取 0～ 1 0 ,1 1～ 2 0 ,2 1～ 30 ,31～ 4 5 ,4 6～ 6 0 ,6 1～ 90 ,91～1 2 0 d各年龄段大鼠共 35只 ,分别腹腔内注射氯胺酮 80 .0 mg/ kg。2 4 h后取鼠脑 ,应用免疫组化染色检测大鼠海马中热休克蛋白 70 (HSP70 )的表达 ,并用 MIAS- 2 0 0 0图像分析系统分析大鼠海马 HSP70阳性细胞百分率、密度和灰度值。结果　氯胺酮可诱导成年大鼠海马神经细胞表达 HSP70。氯胺酮剂量在 80 .0 m g/ kg以内 ,随剂量的增加 ,HSP70阳性细胞密度、百分率和反应强度均显著增加 (P<0 .0 1 ) ;氯胺酮剂量在 80 .0 m g/ kg以上 ,随剂量的增加 ,HSP70阳性细胞密度、百分率和反应强度显著降低 (P<0 .0 1 )。氯胺酮不能诱导 2 0 d以下的幼鼠神经细胞表达HSP70 ;2 0～ 90 d大鼠 ,随着年龄的增加 ,HSP70表达增强 ;90 d以上的大鼠神经细胞 HSP70的阳性表达无显著性差异。结论　氯胺酮可诱导 HSP70在大鼠海马中表达 ,提示海马的神经元可能受到损害 ;随剂量的增加 ,其损害作用加强 ;氯胺酮对成年大鼠的脑损害作用较幼鼠强

Expression of HSP70 Induced by Ketamine in the Hippocampus of Rat at Different Ages

Objective This experiment was designed to explore the possible mechanism of the brain injury caused by ketamine. Methods Thirty five adult SD rats randomly divided into a control group and 6 experiment groups were given intrapertioneal injections of normal saline, 20.0, 40.0, 60.0, 80.0, 100.0, 120.0 mg/kg of ketamine respectively. Another 35 SD rats at 0 10,11 20,21 30,31 45,46 60,61 90,91 120 days old were allocated to 7 corresponding age groups and were given intrapertioneal injection of ketamine 80.0 mg/kg. Immunocytochemistry was used to detect HSP70 expression in rat hippocampus, and MIAS 2000 photography analytic software was chosen to analyze HSP70 expression. Results Ketamine induced HSP70 expression in adult rat hippocampus. Below the dose of 80.0 mg/kg, ketamine induced higher level of HSP70 expression as the dose increased; however, above the dose of 80.0 mg/kg, ketamine induced lower level of HSP70 expression as the dose increased. Ketamine did not induce HSP70 expression in the rats under 20 days of age; it induced the same HSP70 expression in rats of 90 days and over; and analyses of the rats of 20 90 days revealed that the elder the rat is, the higher the HSP70 expression will be. Conclusion Ketamine injures the neurons of rat hippocampus and induces the expression of HSP70, and the higher the dose is given, the more serious the injury is seen; and ketamine induces higher level of HSP70 expression in adult rats than in infant rats.