摘要
目的观察亚低温联合红景天苷对大鼠脑缺血/再灌注后氧化应激和血脑屏障的影响,探讨其内在机制。方法将60只成年雄性SD大鼠随机分为假手术组、模型组、亚低温组、红景天苷组、联合治疗组,每组12只大鼠。假手术组只暴露而不阻断动脉,其余各组均采用改良Pulsinelli 4-VO法制备全脑缺血模型,并于缺血10 min后进行再灌注。再灌注开始前,红景天苷组和联合治疗组大鼠腹腔注射红景天苷(20 mg/kg),假手术组、模型组和亚低温组大鼠腹腔注射等体积生理盐水;使用冰袋诱导低温,使亚低温组和联合治疗组大鼠体温降至(33.0±0.3)℃并维持3 h,假手术组、模型组和红景天苷组大鼠体温维持于(37.0±0.5)℃。再灌注24 h后根据神经功能缺损程度评分量表(NDS)测定各组大鼠的神经功能受损程度,采用干湿重法测量脑组织含水量,伊文思蓝法测量血脑屏障通透性,采用WST-8法测量超氧化物歧化酶(SOD)活力,硫代巴比妥酸法测定丙二醛(MDA)含量,Western Blot法测量基质金属蛋白酶9(MMP9)表达水平。结果与假手术组比较,模型组NDS评分、SOD活力明显降低(P<0.05),脑含水量、脑伊文思蓝含量、MDA含量及MMP9表达量升高(P<0.05)。亚低温组、红景天苷组、联合治疗组NDS评分、SOD活力较模型组升高,联合治疗组较亚低温组、红景天苷组升高(P<0.05);亚低温组、红景天苷组、联合治疗组脑含水量、脑伊文思蓝含量、MDA含量及MMP9表达量较模型组下降(P<0.05),联合治疗组较亚低温组、红景天苷组下降(P<0.05)。结论亚低温联合红景天苷可以抑制全脑缺血/再灌注后的氧化应激反应,改善血脑屏障的通透性,减轻脑水肿,这可能与其降低MMP9表达有关。
Objective To observe the effect of mild hypothermia combined salidroside on oxidative stress(OS)and blood-brain barrier(BBB)of rats after cerebral ischemia/reperfusion(I/R),and to study its internal mech-anism.Methods Sixty male adult Sprague-Dawley rats were randomly divided into five groups,i.e.,the sham-opera-tion group,the model group,the mild hypothermia group,salidroside treatment group,and the combined treatment group,12 rats in each group.Rats in the sham-operation group,the vertebral artery and the common carotid artery were only exposed,but not coagulated.The global cerebral I/R model was established in rats of the rest groups by improved Pusinelli 4-VO method,and I/R was performed after 10-min ischemia.Before starting I/R,salidroside(20 mg/kg)was intraperitoneally injected to rats in salidroside treatment group and the combined treatment group.Equal volume of normal saline was intraperitoneally injected to the rest three groups.The rectal temperature of rats in the mild hypother-mia group and the combined treatment group were reduced to(33.0±0.3)℃with ice bag and maintained for 3 h.In parallel,the rectal temperature of the sham-operation group,the model group,and salidroside treatment group were maintained at(37.0±0.5)℃.After 24-h I/R the degree of neural dysfunction was measured by neurologic deficit scale(NDS).Brain water content was determined by wet and dry weight method.The permeability of blood-brain barri-er(BBB)was determined by Evans blue(EB)method.The activity of SOD was determined by WST-8 method and the content of MDA was determined by thiobarbital acid method.Western Blot was used to measure the expression of matrix metalloproteinase-9(MMP9).Results The NDS score and SOD activity were significantly lower in the model group than in the sham-operation group(P<0.05).The brain water content,EB content,MDA content,and MMP9 expression were also significantly higher in the model group than in the sham-operation group(P<0.05).The NDS score and SOD activity were significantly higher in the mild hypothermia group,salidroside treatment group,and the combined treatment group than in the model group(P<0.05).Changes of these indices were higher in the combined treatment group than in the mild hypothermia group and salidroside treatment group(P<0.05).The brain water con-tent,EB content,MDA content,and MMP9 expression decreased more in the mild hypothermia group,salidroside treatment group,and the combined treatment group than in the model group(P<0.05).They decreased more obvi-ously in the combined treatment group than in the mild hypothermia group and salidroside treatment group(P<0.05).Conclusion Mild hypothermia combined salidroside inhibited global I/R induced oxidative stress,improved the per-meability of BBB,and reduced brain edema,which was possibly related to lowering MMP9 expression.
作者
陈佳艺
董河
冯伟
祝琳
任悦义
王士雷
褚海辰
CHEN Jia-yi;DONG He;FENG Wei;ZHU Lin;REN Yue-yi;WANG Shi-lei;CHU Hai-chen(Department of Anesthesiology,Affiliated Hospital of Qingd-ao University,Shandong,266000;Department of Anesthesiology,Qingdao Women's and Children Hospital,Shan-dong,266034)
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2020年第5期589-594,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(No.81771415)。
关键词
脑缺血/再灌注
红景天苷
亚低温
氧化应激
血脑屏障
cerebral ischemia/reperfusion
salidroside
mild hypothermia
oxidative stress
blood-brain barrier
