丹参酮ⅡA对脑缺血再灌注损伤大鼠磷酸化p38MAPK和MMP-9表达及细胞凋亡的影响  

Effects of Tanshinone ⅡA on expressions of phosphorylated p38MAPK and MMP-9 and neural cell apoptosis following cerebral ischemic reperfusion injury in rats

作　　者：李浩[1] 张多斌[1] 吴岚[1] 冯华坤[1] 

机构地区：[1]桂林医学院附属医院神经内科,广西桂林541002

出　　处：《中风与神经疾病杂志》2013年第3期229-233,共5页Journal of Apoplexy and Nervous Diseases

基　　金：广西自然科学基金资助(桂科自0848015);广西卫生厅科研课题基金资助(Z2007219);广西教育厅高校立项项目(桂教科研201106LX360)

摘　　要：目的探讨丹参酮ⅡA(Tanshinone,TanⅡA)对缺血再灌注(IR)损伤大鼠细胞凋亡和血脑屏障通透性的影响及与p38MAPK通路的关系。方法 60只大鼠随机分为假手术组(Sham组)、缺血再灌注组(IR组)、TanⅡA低剂量治疗组、TanⅡA高剂量治疗组,线栓法建立局灶性脑缺血再灌注模型。TanⅡA高、低剂量组于术前连续灌胃给予高、低剂量TanⅡA 3d,每日1次。各组于脑缺血120min再灌注24h,采用免疫组化法观察大鼠额顶部皮质磷酸化p38MAPK和MMP-9表达;TUNEL法检测神经细胞凋亡,检测伊文斯蓝(EB)含量变化。结果(1)与Sham组相比,IR组磷酸化p38MAPK和MMP-9明显升高(P<0.05);与IR组比较,TanⅡA高、低剂量治疗组磷酸化p38MAPK和MMP-9表达均降低,且高TanⅡA组明显低于低TanⅡA组(P均<0.05);(2)与Sham组相比,IR组凋亡细胞明显增加;与IR组比较,TanⅡA高、低剂量治疗组凋亡细胞均减少,且高TanⅡA组明显低于低TanⅡA组(P均<0.05)。(3)与Sham组比较,IR组脑组织EB含量明显升高;与IR组比较,TanⅡA高、低剂量治疗组脑组织EB含量明显降低(P<0.05),且高TanⅡA组明显低于低TanⅡA组(P均<0.05)。结论 TanⅡA减少脑缺血再灌注后细胞凋亡,抑制MMP-9表达降低血脑屏障通透性,可能与抑制p38MAPK信号通路有关。Objective To study effects of Tanshinone Ⅱ A （Tan Ⅱ A）on neural cell apoptosis and the permeability of the blood-brain barrier following cerebral ischemia reperfusion （IR） injury rats, and explore the releationship between theirs and p38 mitogen-activated protein kinase pathway. Methods 60 SD rats were randomly divided into four groups, which were sham operated group, IR group,low dose TanⅡ A treated group and high dose Tan Ⅱ A treated group. The focal middle cerebral artery occlusion （MCAO）model was made in rats with suture-occluded method. Low dose and high dose groups were pretreated with low and high does Tan Ⅱ A,for 3d, before MCAO. After 120min MCAO following 24h reperfu- sion,We investigated the expressions of phosphorylated p38MAPK and MMP-9 in using immunohistochemistry technique in the frontal and parietal cortex. Neural cell apoptosis was investigated with TUNEL. The contents of Evens blue （EB） was also investigated. Results （1）Compared with sham operated group, phosphorylated p38MAPK and MMP-9 increased in IR group ; Compared with IR group, high and low dose Tan Ⅱ A treated groups dose-dependently decreased expression of phosphorylated p38MAPK and MMP-9 （P 〈 0.05 ） ;（2）Compared with sham operated group, cell apoptosis was distinctly increased in IR group;Compared with IR group, Compared with that of I/R group,low and high Tan Ⅱ A treated group dose- dependently reduced neural cell apoptosis （all P 〈 0.05 ）. （3）Compared with sham operated group, the contents of EB in- creased at 24h of reperfusion. Compared with I/R group,low and high Tan Ⅱ A treated group dose-dependently reduced the contents of EB （ all P 〈 0.05 ）. Conclusion Tan Ⅱ A may attenuate neural cell apoptosis and reducing the expression of MMP-9 to protects blood-brain barrier by inhibiting p38 mitogen-activated protein kinase pathway.

关 键 词：缺血再灌注 磷酸化P38MAPK MMP-9 凋亡 血脑屏障 丹参酮ⅡA 

分 类 号：R743.3[医药卫生—神经病学与精神病学]