摘要
目的探讨丙泊酚对2型糖尿病大鼠认知功能的影响并研究其潜在机制。方法健康雄性成年SD大鼠50只,其中10只采用普通饲料正常喂养作为空白对照组,40只采用高脂高糖饲料喂养8周联合一次性注射1%STZ建立糖尿病模型,并分为四组:糖尿病组和低、中、高剂量丙泊酚组,糖尿病大鼠分别腹腔注射1%丙泊酚10、30、75mg·kg^(-1)·d^(-1),连续注射5d。丙泊酚用药后第1天开始采用Morris水迷宫实验检测大鼠逃避潜伏期和穿越原平台次数;HE染色观察大鼠海马组织病理变化;采用比色法检测脑组织匀浆中超氧化歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-PX)浓度;Western blot检测大鼠脑组织中晚期糖基化终产物(AGEs)及其受体(RAGE)蛋白含量。结果与空白对照组比较,糖尿病组大鼠逃避潜伏期明显延长,穿越原平台次数明显减少,神经元细胞损伤明显增加,SOD、CAT、GSH和GSHPX浓度明显降低,MDA浓度明显升高,AGEs和RAGE蛋白含量明显升高(P<0.05);与糖尿病组比较,低剂量丙泊酚组大鼠逃避潜伏期和穿越原平台次数差异无统计学意义,中、高剂量丙泊酚组大鼠逃避潜伏期明显延长,穿越原平台次数明显减少,SOD、CAT、GSH和GSH-PX浓度明显降低,MDA浓度明显升高,同时AGEs和RAGE蛋白含量明显升高(P<0.05)。结论镇静和麻醉剂量的丙泊酚能够加重糖尿病大鼠的认知功能障碍,加重氧化应激反应,这可能与上调脑组织中AGEs/RAGE蛋白含量有关。
Objective To explore the effects and mechanism of propofol on cognitive function of type 2diabetic rats.Methods Ten of fifty adult male SD rats were fed with basic diet and allocated to control group.Another forty rats were fed with high sugar and high fat for 8weeks and composite intraperitoneal injection of 1% streptozotocin（STZ）to establish model and then divided into four groups：diabetes group;low dose,middle dose and high dose of propofol group（diabetic rats were given intraperitoneal injection of 1% propofol 10,30,75mg·kg^-1·d^-1 for 5consecutive days）.The cognitive functions were examined by Morris water maze from the first day after intraperitoneal injection with propofol.The hippocampus were isolated for observing histopathologic alterations by HE staining and for the determinations of SOD, MDA,CAT,GSH and GSH-PX by colorimetry.Western blot was used to detect the expression of AGEs and RAGE.Results Compared to the control group,there was an obvious increased escape latent period,decreased the frequency of crossing platform,increased hippocampal neurons damage and MDA,decreased levels of SOD,CAT,GSH and GSH-PX,as well as the protein levels of AGEs and RAGE in diabetes group（P〈0.05）.There was no significant difference between diabetes group and low dose propofol of group on behavior ability and detection index.However,middle dose and high dose of propofol group showed more serious cognitive dysfunction,aggravated hippocampal neurons cells loss,increased oxidative stress as well as enhanced expression of AGEs and RAGE（P〈0.05）.Conclusion Multiple given sedative or anesthetic doses of propofol can aggravate the cognitive dysfunction and oxidative stress in type 2diabetic rats,which may be related to increase the expression of AGEs and RAGE in brain tissue.
作者
梁冰
董铁立
LIANG Bing DONG Tieli(Department of Anesthesiology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Chin)
出处
《临床麻醉学杂志》
CAS
CSCD
北大核心
2017年第9期904-908,共5页
Journal of Clinical Anesthesiology
关键词
丙泊酚
糖尿病
认知功能
Propofol
Diabetis
Cognitive function
