脑缺血再灌注损伤后血脑屏障结构与功能的变化及丁苯酞预处理的干预作用

 目的:探讨脑缺血再灌注损伤（CIRI）大鼠血脑屏障结构与功能的变化，以及丁苯酞（NBP）预处理对其的干预作用。 方法: 120只雄性SD大鼠随机分为假手术组（sham组）、模型组（IR组）、NBP预处理组低剂量组（NBPⅠ组）、NBP预处理组中剂量组（NBPⅡ组）和NBP预处理组高剂量组（NBP Ⅲ组），每组24只。采用线栓法制作CIRI模型，缺血2 h再灌注24 h后测定脑含水量和伊文思蓝（EB）含量，透射电镜下观察血脑屏障病理形态学变化，分别采用免疫组化法和real-time PCR法检测基质金属蛋白酶9（MMP-9） 蛋白和mRNA的表达。 结果: 脑缺血再灌注损伤后脑水肿加重，EB含量明显增加，血脑屏障损伤严重，MMP-9表达上调（均P<0.01）；NBP预处理后能明显减轻脑水肿，减少EB含量，减轻血脑屏障损伤，降低MMP-9的表达（均P<0.01）；NBPⅡ、Ⅲ组较NBPⅠ组改变更为明显（P<0.05），Ⅱ、Ⅲ组之间差异无统计学意义（P＞0.05）。 结论: 丁苯酞预处理脑缺血再灌注损伤大鼠后，可降低MMP-9的表达，减轻血脑屏障损伤程度，发挥预防性保护作用。

Effect of 3-n-butylphthalide pretreatment on structure and function chan-ges of blood brain barrier in rat model of focal cerebral ischemia-reperfusion injury

AIM: To investigate whether pretreatment with 3-n-butylphthalide (NBP)  ameliorates blood brain barrier (BBB) dysfunction in a rat model of focal cerebral ischemia-reperfusion injury (CIRI). METHODS: Male SD rats (n=120, 24 rats in each group) were randomly divided into sham operation group (sham group), model group (IR group), low dose group of NBP pretreatment (NBP I group), medium dose group of NBP pretreatment (NBP II group) and high dose group of NBP pretreatment (NBP III group). The model of CIRI was established by a suture method. After ischemia for 2 h and reperfusion for 24 h, the contents of water and Evans blue (EB) were detected. The pathological changes of the BBB ultrastructure were observed under transmission electron microscope. The protein level of matrix metalloproteinases 9 (MMP-9) was measured by immunohistochemical technique. The mRNA expression of MMP-9 was determined by real-time  PCR. RESULTS: After CIRI, the content of water and EB was progressively increased, the BBB was damaged seriously, and the expression of MMP-9 was significantly up-regulated compared with sham group (all P<0.01). Pretreatment with NBP significantly decreased the contents of water and EB, relieved morphological damage of the BBB, and reduced the expression of MMP-9 obviously (all P<0.01). Compared with NBP I group, the changes in NBP II and III group were remarkable (P<0.05), but the difference between NBP II group and NBP III group was not obvious (P＞0.05). CONCLUSION: Pretreatment of 3-n-butylphthalide has preventive effect against cerebral ischemia reperfusion injury in the rats, which may be related to decrease the expression of MMP-9 and reduce the permeability of blood brain barrier.