紫菜多糖对脑缺血再灌注损伤小鼠血脑屏障的保护作用  

Protective effects of Porphyra polysaccharide on blood brain barrier following focal cerebral ischemia/reperfusion in mice

作　　者：葛建彬[1,2] 宋新建[1] 陈丹丹 李梅[2] 顾锦华[3] GE Jian-bin;SONG Xin-jian;CHEN Dan-dan;LI Mei;GU Jin-hua(Department of Pharmacy,The Second People＇s Hospital of Nantong,Nantong 226002,Jiangsu Province,China;Department of Pharmacology,College of Pharmaceutical Science,Soochow University,Sugtou 215123,Jiangsu Province,China;Department of Pathophysiology,Medical College of Nantong University,Nantong 226001,Jiangsu Province,China)

机构地区：[1]南通市第二人民医院药剂科,江苏南通226002 [2]苏州大学药理教研室,江苏苏州215123 [3]南通大学病理生理教研室,江苏南通226001

出　　处：《中国临床药理学杂志》2018年第19期2291-2294,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(31500822);南通市卫生局青年科研基金资助项目(WQ2014027)

摘　　要：目的研究紫菜多糖对小鼠脑缺血再灌注损伤后血脑屏障的影响。方法将180只雄性ICR小鼠随机分为假手术组、模型组、对照组和低、中、高剂量实验组,每组30只。模型组、对照组和实验组用线栓法制作小鼠短暂性大脑中动脉阻塞(t MCAO)模型,假手术组接受相似手术处理,但是不插入线栓。对照组在造模前腹腔注射4 mg·kg^(-1)尼莫地平,低、中、高剂量实验组在造模前分别给予100,200,400 mg·kg^(-1)紫菜多糖,连续注射7 d,每天1次;假手术组和模型组腹腔注射等量生理盐水。观察各组小鼠的脑梗死范围、脑含水量,用伊文思蓝(EB)法观察小鼠血脑屏障通透性的改变,用Western blot法检测缺血大脑皮层基质金属蛋白酶-9(MMP-9)和胞浆附着蛋白-1(ZO-1)蛋白的表达。结果模型组和低、中、高剂量实验组小鼠脑梗死体积分别为(28.45±5.32)%,(24.73±3.65)%,(22.36±4.19)%和(18.61±5.72)%;脑含水量分别为(83.23±1.56)%,(80.72±1.17)%,(80.38±1.32)%和(79.59±1.41)%;脑组织EB含量分别为(8.02±0.71),(7.18±0.66),(4.75±0.73)及(3.93±0.64)μg·g^(-1);缺血侧大脑皮层MMP-9蛋白水平为0.65±0.09,0.52±0.11,0.39±0.08和0.31±0.07;缺血侧大脑皮层ZO-1蛋白水平分别为0.18±0.07,0.24±0.06,0.37±0.08和0.51±0.10,差异均有统计学意义(均P<0.05)。结论紫菜多糖通过下调脑缺血再灌注后脑组织中MMP-9的表达,上调ZO-1的表达,降低血脑屏障通透性,这可能是紫菜多糖保护缺血再灌注后脑损伤的机制之一。Objective To study the effect of Porphyra polysaccharide on blood- brain barrier after cerebral ischemia -reperfusion in mice. Methods A total of 180 male ICR mice were randomly divided into sham operation group, model group, control group and low, middle and high dose experimental groups, 30 mice in each group. The transient middle cerebral artery occlusion （tMCAO） model was established by the method of suture thread in model group, control group and experimental groups. The sham operation group received similar surgical treatment but no line thrombectomy was performed. Control group was intraperitoneally injected 4 mg·kg^-1 nimodipine before modeling, low, middle and high dose experimental groups were intraperitoneally injected 100, 200, 400 mg·kg^-1 Porphyra polysaccharide, once a day, continuously for 7 d.Sham group and model group were intraperitoneally injected with normal saline. The cerebral infarct size and brain wa- ter content of the mice in each group were observed. The permeability of the blood - brain barrier was observed by Evans blue （ EB ） method. The expressions of matrix metalloproteinase - 9 （ MMP - 9 ） and zonula occludens - 1 （ZO - 1 ） protein in ischemic cerebral cortex were detected by Western blot. Results The volume of cerebral infarcz tion in model group and low, middle, high dose experimental groups were （ 28.45 ± 5.32 ） %, （ 24.73±3±65 ） %, （22.36±4.19）%, （18.61±5.72）%; brain water content were （83.23 ± 1.56）%, （80.72± 1.17）%, （80. 38 ±1.32） %, （79.59 ±1.41 ） % ; brain EB content were （81 02 ±0.71 ）, （7.18 ± 01 66）, （4.75 ± 0.73 ） and （3.93 ± 0. 64） μg ·g-1 the levels of MMP - 9 protein in ischemic cerebral cortex were 0. 65 -0. 09, 0. 52±0. 11 0. 39±0. 08 and 0. 31±0. 07; the levels of ZO -1 protein in cerebral cortex were 0. 18 ±0. 07, 0. 24 ±O. 06, 0. 37±0. 08 and 0. 51 ± 0. 10, all with significant differences （ all P 〈 0. 05 ）. Conclusion Porphyra polysaccharide can down - regulate the e

关 键 词：紫菜多糖 脑缺血再灌注 血脑屏障 基质金属蛋白酶-9 胞浆附着蛋白 

分 类 号：R28[医药卫生—中药学]