糖尿病大鼠脑额叶皮层血流量的经时变化

摘要

目的 探讨糖尿病大鼠脑额叶皮层血流量的动态变化,初步研究其与主要血管活性物质变化的关系,为进一步研究糖尿病认知障碍以及中枢神经系统功能变化提供前期基础.方法 34只♂ Wistar大鼠随机分为空白对照组和糖尿病模型组.模型组腹腔注射链脲佐菌素(STZ) 60 mg·kg-1复制糖尿病模型,葡萄糖氧化酶法测定72 h空腹血糖≥16.7 mmol·L-1作为成模标准,血糖仪连续动态测定FBG,Moms水迷宫检测糖尿病大鼠学习记忆能力,双通道激光多普勒血流仪检测大鼠90 d额叶皮层血流量.另取34只♂ Wistar大鼠分组造模同前,连续动态监测造模d0、7、14、21、28、35、42、56、75额叶皮层血流量;ELISA法检测脑脊液中iNOS、cNOS和ET-1的浓度.结果 Morris水迷宫检测显示,糖尿病模型组大鼠从训练第6次逃避潜伏期明显延长(P＜0.05),额叶皮层血流量/100 g体重明显降低(P＜0.05);额叶皮层血流量动态监测结果显示,糖尿病大鼠造模d 21脑血流量/100 g体重下降(P＜0.05),并在相似水平持续到成模d 75(P ＜0.01,P ＜0.05);与对照组相比,模型组脑脊液中iNOS和cNOS浓度明显升高(P＜0.05),ET-1浓度明显下降(P＜0.01).结论 糖尿病认知障碍大鼠额叶皮层血流量减少,提示脑血流量的减少可能是导致糖尿病发生认知障碍的因素之一.糖尿病动态脑血流量检测显示脑血流量减少发生在糖尿病早期,之后并无明显继续恶化.脑血流减少可能与NO、ET-1浓度变化无明显关系,但脑血流的变化趋势可能与二者变化有关.%Aim To investigate the changes of cerebral blood flow in rats with diabetic cognitive impairment by two-channel laser Doppler flowmeter,and to explore the changes of cerebral blood flow in diabetic rats with cognitive impairment and to investigate the changes of cerebral blood flow lesions and the central nervous system function changes in the study to provide pre-foundation.Methods Thirty-four male Wistar rats were randomly divided into two groups:blank control group and diabetic model group.The rats in the model group were treated with streptozotocin (STZ) 60 mg · kg-1,and the glucose oxidase method was used to determine fasting blood glucose ≥ 16.7 mmol · L-1 as the standard of the model.The Water maze was used to observe the behavioral changes of diabetic rats.Dual-channel laser doppler flowmeter was used to measure cerebral blood flow in diabetic rats with cognitive impairment.Another 34 male Wistar rats were randomly divided into two groups:control group and diabetic model group.Dual-channel laser doppler flowmeter was used to dynamically monitor cerebral blood flow on 0 d,7 d,14 d,21 d,28 d,35 d,42 d,56 d and 75 d.ELISA was applied to detect the concentration of iNOS,eNOS and ET-1 in cerebrospinal fluid.Results Morris water maze test showed that the time of the platform (latency) was significantly longer than that of the blank control group(P ＜0.05).The cerebral blood flow/100 g of diabetic rats with cognitive impairment was significantly lower than that of the control group (P ＜ O.05),and the blood flow in the model group was significantly lower than that in the model group (P ＜ 0.05).Compared with control group,iNOS and eNOS concentrations were markedly elevated,while ET-1 concentration obviously decreased.Conclusions The decrease of blood flow in the frontal cortex of diabetic rats with cognitive impairment suggests that it may be one of the factors leading to cognitive impairment in diabetes mellitus.Cerebral blood flow reduction occurs in the early stages of diabetes,followed by no significant deterioration.Cerebral blood flow may not be related to the changes of NO and ET-1,but the trend of cerebral blood flow may be related to the change of the two.