康脑液对脑缺血大鼠BDNF,MMP-9,ERK1/2表达的影响

Effect of Kangnaoye on Expressions of BDNF,MMP-9,ERK1 /2 on Cerebral Ischemia Reperfusion in Rats

目的:通过康脑液干预观察其对脑缺血再灌注大鼠脑源性神经生长因子(BDNF),基质金属蛋白酶-9(MMP-9),细胞外信号调节激酶(ERK1/2)表达的影响,探讨康脑液对脑缺血的保护机制。方法:将雄性SD大鼠随机分为假手术组、脑缺血再灌注模型组(I/R)及康脑液高、中、低剂量(28.6,14.3,7.15 g·kg-1·d-1)组,线栓法制备大鼠右侧大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)再灌注模型。于缺血2 h后再灌注(分别于再灌注后1,6,12,24,72,168 h后,处死大鼠),用免疫组织化学法观察大鼠脑组织BDNF,MMP-9,ERK1/2的表达情况。结果:与I/R组比较,康脑液高、中剂量组各时间点的BDNF及ERK1/2表达量明显上调(P<0.05),而MMP-9表达的阳性细胞明显减少(P<0.05);再灌注24 h梗死灶体积康脑液高,中剂量组较I/R组明显减小(P<0.05)。结论:康脑液可促进大鼠局灶性脑缺血后脑组织中BDNF的表达,激活ERK1/2信号通路,同时抑制脑内MMP-9的表达,发挥对神经血管单元的保护作用。

Objective： To observe the effect of Kangnaoye on the expression of brain derived neurotrophic factor （BDNF）, matrix metalloproteinase-9 （MMP-9）, extracellular signal regulated kinase 1/2 （ERK1/2） in rat with cerebral ischemia reperfusion injury, and to study its cerebral protection mechanism. Method： Male SD rats were randomly divided into the sham-operation group, the ischemia reperfusion （I/R） group, the high-, medium-, and low-dose Kangnaoye groups （28.6, 14.3, 7.15 g ·kg^-1·d^-1）. The cerebral ischemia reperfusion model was prepared in rats by a improved Zea Longa method. The rats were killed at 1-, 6-, 12-, 24-, 72- and 168-h reperfusion after 2-h ischemia. The expression of BDNF, MMP-9 and ERK1/2 were observed by using immunohistochemical method. Result： Compared with I/R group, the expression of BDNF and ERK1/2 was upregulated, the numbers of MMP-9 positive cells decreased in the high- and medium-dose Kangnaoye groups （P 〈 0.05 ）. Moreover, the infarct volume decreased significantly at 24-reperfusion （ P 〈 0.05 ）. Conclusion： Kangnaoye could protect neurovascular unit by promoting the expression of BDNF in brain tissue, activating ERK1/2 signaling pathway, and inhibiting the expression of MMP-9.