阿托伐他汀对局灶性脑缺血大鼠MMP-2 occludin mRNA的影响

Impact of atorvastat on MMP-2 and occludin mRNA in focal cerebral ischemia rats

目的观察局灶性脑缺血大鼠IgG、MMP-2、occludin mRNA的动态变化,探讨阿托伐他汀对其的影响。方法选用雄性SD大鼠108只,随机分为假手术组、模型组、治疗组,采用左侧大脑中动脉栓塞法制备局灶性脑缺血模型,以术后1、3、7d为观察时间点。治疗组给予阿托伐他汀4mg/(kg·d)灌胃,其余2组在相应时间给予等量生理盐水灌胃。观察各组大鼠IgG、MMP-2、occludin mRNA在各时间点的动态变化,评估血脑屏障变化情况。免疫组化法检测IgG、MMP-2,RT-PCR检测occludin mRNA。结果与假手术组相比,模型组和治疗组在各时间点IgG、MMP-2增加,而occludin mRNA表达减少,均在第3天达峰,且差异有统计学意义(P<0.05)。与模型组相比,治疗组在各时间点IgG、MMP-2降低,而occludin mRNA表达增加,且差异有统计学意义(P<0.05)。结论局灶性脑缺血大鼠血脑屏障通透性增加,在第3天最严重;阿托伐他汀可能通过抑制MMP-2活性,提高occludin mRNA表达,降低血脑屏障通透性,起到脑保护作用。

Objective To observe the changes of IgG,MMP-2, occludin mRNA, and to investigate the impact of atorvastatin on IgG, MMP-2, occludin mRNA of focal cerebral ischemia rats. Methods One hundred and eight male SD rats were randomly divided into sham operation group, model group and treatment group, the focal cerebral ischemia model was induced by left middle cerebral artery occlusion, the observing time was 1d, 3d, 7d after operation. The treatment group received a gavage of atorvastatin 4mg/（kg·d）, others were given the same amount of normal saline at corresponding time. The changes of IgG, MMP-2, occludin mRNA in each group were observed at each observing time to assess the changes in the blood-brain barrier. The expression of IgG, MMP-2 was analyzed by immunohistochemistry, the expression of occludin mRNA was analyzed by RT-PCR. Results Compared with the sham operation group, IgG, MMP-2 in both model group and treatment group increased at each observing time, but occlu- din mRNA expression decreased at each observing time, all of them reached the peak at 3d, the differences were all statistically sig- nificant （P〈0. 05）. Compared with the model group, IgG, MMP-2 of treatment group decreased at each observing time, but occludin mRNA expression increased at each observing time, the differences were all statistically significant （P〈0.05）. Conclusion The permeability of blood-brain barrier in focal cerebral ischemia rats was increased, and reached the peak at 3d; atorvastatin can inhibit the activity of MMP-2, and increase the expression of occludin mRNA to reduce the permeability of blood-brain barrier and protect brain tissue.