SB203580对脑缺血再灌注损伤后基质金属蛋白酶9表达的影响

SB203580 affects the expression of matrix metalloproteinase-9 after cerebral ischemia-reperfusion injury in rats with hyperlipemia

目的:通过检测抑制剂SB203580对缺血侧大脑皮质p38丝裂原活化蛋白激酶(p38MAPK)和基质金属蛋白酶9(MMP-9)表达的影响,探讨p38MAPK是否可以影响MMP-9的表达而参与高血脂加重脑缺血再灌注损伤。方法:喂食高脂饲料建立高脂血症动物模型,模型成功后随机分为抑制剂SB203580预处理的脑缺血2h再灌注24h组(SB组)、DMSO组、sham+SB组和sham+DMSO组,然后采用线栓法建立脑缺血再灌注模型。神经行为学评分观察神经行为损伤症状,TTC染色检测梗死灶体积,伊文思蓝染色检测血脑屏障通透性,免疫印迹检测p38MAPK和MMP-9表达水平,反转录PCR检测MMP-9mRNA水平。结果:与假手术组比较,SB组和DMSO组p38MAPK和MMP-9表达均明显增高。与DMSO组比较,SB组p38MAPK和MMP-9表达明显降低,差异有统计学意义。且SB组MMP-9mRNA水平较DMSO组明显降低,神经行为损伤程度、梗死灶体积和血脑屏障通透性亦明显降低,差异均有统计学意义。结论:高脂血症脑缺血再灌注损伤中,p38MAPK可上调MMP-9表达,促进细胞凋亡的发生及增加血脑屏障通透性,进而加重脑缺血再灌注损伤。

Objective： To discuss if p38MAPK affecting MMP-9 expression induce hyperlipemia attending the aggravation of ischemia-reperfusion injury by detecting the effect of SB203580 on the expression of p38MAPK and MMP9. Methods： The hyperlipemia rats model was made with home-made high-fat diet. Then the hyperlipemia rats were randomly divided into SB group, DMSO group, shamq-SB group and sham4-DMSO group. The focal cerebral ischemia-reperfusion model was established with thread embolism of the middle cerebral artery. The neurobehavioral changes of rats were observed using neurological behavioral evaluation. TTC staining was employed to assess the cerebral infarct volume. EB staining was employed to detect the blood-brain barrier permeability. Western blotting was used to examine the expression of p38MAPK and MMP-9 in the cerebral cortex, and reverse transcription-polymerase chain reaction was used to detect the level of MMP-9 mRNA. Results： Compared with shamq-SB and shamq-DMS0 group, the expressions of p38MAPK and MMP-9 significantly increased in the SB group and DMSO group. However, the expression of p38MAPK and MMP-9 was significantly lower in the SB group than that in the DMSO group. The level of MMP-9 mRNA in SB group was significantly lower than that in the DMSO group. Compared with the DMSO group, the degree of neurobehavioral damage, infarct volume and blood-brain harrier permeability was also significantly reduced in the SB group. Conclusion： In cerebral ischemia-reperfusion injury rats with hyperlipemia, p38MAPK can increase the expression of MMP-9, which aggravates cerebral ischemia-reperfusion injury by promoting apoptosis and increasing blood-brain barrier permeability.