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.