Dose-effect dependence of ketamine in inducing the expression of heat shock protein 70 in the hippocampus of rats of different ages / 中国组织工程研究

ABSTRACT

BACKGROUND: It is proved that protein of heat shock protein 70 family has protective effects on cells. Ketamine can cause psychiatric symptoms such as illusion and delirium in patients, which can damage neurons of the limbic system in rats. The expression of heat shock protein 70 can be detected in the damaged neurons with immunohistochemical staining.OBJECTIVE: To observe the expression of heat shock protein 70 induced by ketamine in the hippocampus of rats of different ages and probe into the damaging effect on nerves.DESIGN: Randomized controlled trial.SETTING: Department of Anesthesiology and Critical Care Medicine,Huaxi Hospital of Sichuan University.MATERIALS The experiment was conducted in the laboratory of the Department of Anesthesiology and Critical Care Medicine, Huaxi Hospital of Sichuan University, from January to May 2001. Totally 70 SD rats,weighing 25 to 285 g, of either gender and clean grade, were recruited.Thirty-five adult SD rats were randomly divided into control group and ketamine groups of 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg with 5 rats in each group. The rats in each group were injected intraperitoneally with normal saline and 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg of ketamine, respectively. Another 35 rats aged 0-10, 11-20, 21-30, 31-45,46-60, 61-90 and 91-120 days, 5 rats in each age stage, were given intraperitoneal injection of 80.0 mg/kg ketamine. After 24-hour survival time, the animals were put to death and their brains were removed. 5 μm-thick coronal sections of the hippocampus were cut on a vibratome. The expression of heat shock protein 70 was detected in the hippocampus of rats of different ages with immunohistochemical staining.MAIN OUTCOME MEASURES: Positive cellular percentage, density and grayscale of heat shock protein 70 in the rats' hippocampus.of different doses of ketamine on the expression of heat shock protein in rat hippocampus In control group, the cellular density of heat shock protein 70 expression induced by 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg of ketaminewas0, 8.12±1.82, 27.07±5.98, 45.35±5.84, 78.51±7.34,74.16±8.17 and 60.84±6.27, respectively. It indicated that when ketamine was under 80.0 mg/kg, the cellular density of heat shock protein 70 in creased significantly with the dose increase (P ＜ 0.01). When ketamine was over 80.0 mg/kg, the cellular density significantly decreased with the dose tamine in the hippocampus of rats of different ages The density of positive nerve cells of heat shock protein 70 in young rats aged under 20 days was 0; the density of young rats aged 21-30 days, 31-45 days, 46-60 days and 61-90 days was 34.17±6.18, 55.42±4.80, 78.51±7.34 and 83.16±11.10,respectively. Compared with that of the first age group, with the increased age, the density of positive cells of heat shock protein 70 was significantly increased (P ＜ 0.01); it was 83.16±11.10 and 85.83±9.33 in the hippocampus of rats aged 61-90 days and 91-120 days, re spectively (P ＞ 0.05).CONCLUSION: Ketamine can induce the expression of heat shock protein 70 in the hippocampus of rats, indicating that neurons of the hippocampus may be damaged; with the increase of dose, its damaging effect is enhanced.The damage of ketamine is greater in adult rats than in young rats.