白藜芦醇抑制神经元MMP-9表达的作用机制研究

The mechanism of inhibitive effect of resveratrol on matrix metalloproteinase-9 in neuron

目的白藜芦醇是一类多酚类化合物,研究表明白藜芦醇能通过下调基质金属蛋白酶9(MMP-9)对神经元产生保护作用。对其抑制机制进行探讨。方法以小鼠神经元氧糖剥夺为模型,分别加入不同剂量的白藜芦醇和过氧化物酶体增殖物激活受体(PPAR)α阻断剂MK886,通过测定乳酸脱氢酶活力反映细胞的损伤程度,分别采用蛋白印迹和逆转录聚合酶链反应研究PPAR-α和MMP-9的表达,探讨白藜芦醇、MMP-9和PPAR-α之间的关系。结果白藜芦醇能上调PPAR-α的表达,同时抑制MMP-9的表达,上述作用能被MK886部分阻断。结论白藜芦醇能通过上调PPAR-α抑制MMP-9的表达。

Objective Resveratrol is a kind of natural polyphenol. Experiments confirm that resveratrol can exert protective effects on neurons by doval-regulating matrix metalloproteinase-9 （MMP-9）. Relationship between resveratrol and MMP-9 will be investigated in the study. Methods Relationship between resveratrol, MMP-9 and peroxisome proliferators-activated receptor （PPAR）α was studied in oxygen glucose deprivation （OGD） mouse neuron model. Different doses of resveratrol and PPAR-α antagonist MK886 were added into cultural medium. Neuronal danlage was evaluated by lactate dehydrogenase （LDH） leakage ratio. Western blot and reverse transcription-PCR were carried out to evaluate the expression of PPAR-α and MMP-9. Results It showed that resveratrol could up-regulate the expression of PPAR-α and inhibit mRNA and protein expression of MMP-9. The effect of resveratrol on both PPAR-α and MMP-9 could be partially antagonized by MK886. Conclusion It suggests that resveratrol can inhibit MMP-9 expression by up-regulating PPAR-α.