MRS2179对大鼠缺血性脑卒中后MMP-9表达及血脑屏障通透性的影响  

MRS2179 Reduces the MMP-9 Expression and Blood-brain Barrier Permeability in Rat Brain after Focal Cerebral Ischemia

作　　者：张秋佳[1] 杨锦珊[1] 刘阳[1] 王伟[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030

出　　处：《神经损伤与功能重建》2014年第5期369-372,共4页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金(No.81030021)

摘　　要：目的:观察P2Y1受体抑制剂MRS2179对大鼠缺血性脑卒中后MMP-9表达及血脑屏障(BBB)通透性的影响。方法:45只SD大鼠随机分成假手术组、模型组、MRS2179组各15只。假手术组及模型组经侧脑室注射5μL人工脑脊液(aCSF),MRS2179组侧脑室注射5μL MRS2179(2 nmol)。制备大脑中动脉阻塞(MCAO)模型,假手术组不予缺血。缺血再灌注24 h后,应用干湿重法检测脑组织含水量;伊文思蓝染料(EB)溢出量定量检测BBB通透性改变;Western blot法检测MMP-9蛋白表达。结果:模型组、假手术组、MRS2179组的脑含水量分别为(81.72±0.23)%、(77.65±0.27)%、(79.92±0.24)%(n=6),模型组高于假手术组(P<0.01);MRS2179组较模型组有所下降(P<0.01),但仍高于假手术组(P<0.01)。模型组梗死侧脑组织血管外EB溢出量为(1737.60±67.46)ng/g,显著高于假手术组(324.18±63.35)ng/g(P<0.01);MRS2179组梗死侧脑组织血管外EB溢出量为(1165.15±93.26)ng/g,较模型组明显下降(P<0.01)(n=6)。假手术组、模型组、MRS2179再灌注24 h梗死边缘区脑组织中相对MMP-9蛋白含量分别为(0.52±0.05)、(1.69±0.08)、(0.99±0.10)(n=3),模型组与假手术组相比明显升高(P<0.01),MRS2179组与模型组比较显著下降(P<0.01)。结论:P2Y1R抑制剂MRS2179可能通过降低MMP-9表达,降低BBB通透性,减轻缺血性脑卒中后脑水肿程度。Objective：To observe the effects of selective P2Y1R antagonist, MRS2179, on the expression of MMP-9 and the blood-brain barrier （BBB） permeability in a rat model of middle cerebral artery occlusion（MCAO）. Methods：All 45 SD rats were randomized into 3 groups：sham group （n=15）, model group （n=15）and MRS2179 group （n=15）. Intracerebroventricular administration of 5 μL vehicle control （aCSF） was performed to the sham group and the model group. Meanwhile, 5μL of MRS2179 （2 nmol） was given to the rats in the MRS2179 group in the same way. The MCAO models were made in the groups control and MRS2179.The sham group was treated in the same manner as those undergoing MCAO, however, no occluding thread was inserted. After 24 h reperfu-sion, the wet/dry method was used to evaluate the brain water content of the ischemic hemisphere, the Evans Blue dye （EB） extravasation was measured to assess the BBB permeability and the expression of MMP-9 was deter-mined by Western blot. Results：The brain water content in the model group, the sham group and the MRS2179 group was （81.72＆#177;0.23）%, （77.65＆#177;0.27）%, （79.92＆#177;0.24）%respectively（n=6）. Compared with the model group, the brain water content in the MRS2179 group was decreased, but was still higher than that in the sham group （ ＆lt;0.01） .The EB extravasation from the ischemic hemisphere in the model group was （1737.60＆#177;67.46）ng/g, remarkably higher than those in the in the MRS2179 group [（1165.15＆#177;93.26）ng/g] and sham group [（324.18＆#177;63.35）ng/g] （ ＆lt;0.01） （n=6）. In terms of the expression of MMP-9 in the ischemic penumbra, the protein amount was （0.52＆#177;0.05）, （1.69＆#177;0.08） and （0.99＆#177;0.10） respectively in the sham group, the model group and the MRS2179 group （n=3）. The protein amount in the MRS2179 group was significantly lower than that in the model group （ ＆lt;0.01）. Conclusion：Inhibition of P2Y1R by MRS2179 might reduce t

关 键 词：MRS2179 缺血性脑卒中 血脑屏障 脑水肿 基质金属蛋白酶-9 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.05[医药卫生—临床医学]