Effects of Liangxue Tongyu Formula on brain edema and expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rats with intracerebral hemorrhage / 中西医结合学报

ABSTRACT

Objective: To investigate the effects of Liangxue Tongyu Formula (LXTYF), a compound traditional Chinese herbal medicine, on brain edema in rats with intracerebral hemorrhage and to explore the mechanism. Methods: Intracerebral hemorrhage was induced by using the intrastriatal autologous blood injection. Rats were randomized into sham-operated (SO) group, intracerebral hemorrhage (ICH) group and LXTYF group. Rats in the LXTYF group were intragastrically administered with LXTYF every day while the other two groups were given normal saline. Brain water content was determined at 24, 48, 72, and 120 h after intracerebral hemorrhage. Matrix metalloproteinase-9 (MMP-9) level, and MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expressions in perihematoma area were detected by gelatin zymography and fluorescence quantitative real-time polymerase chain reaction at the four time points, respectively. Results: Water content in the ICH group was highly elevated after intracerebral hemorrhage, and reached to the peak at 72 h. Compared with the ICH group, the LXTYF group had lower water contents at 48, 72 and 120 h after intracerebral hemorrhage (P<0.01). The difference in water content between the LXTYF and SO groups was significant only at 72 h (P<0.01). Although the pro-MMP-9 level and MMP-9 activity in the LXTYF and ICH groups were enhanced, they were still lower in the LXTYF group than in the ICH group (P<0.01 for 24, 48, 72 and 120 h, respectively). And there was no significant difference in them between the LXTYF group and the SO group at 120 h. Meanwhile, MMP-9 mRNA expressions were increased in the ICH and LXTYF groups, but the levels in the LXTYF group were significantly lower (P<0.01 for 48, 72 and 120 h, respectively) than those in the ICH group. Also, TIMP-1 mRNA expressions at 24, 48, 72 and 120 h after intracerebral hemorrhage were up-regulated in the LXTYF group, and there were significant differences in TIMP-1 expressions between the LXTYF group and ICH group after intracerebral hemorrhage (P<0.01). Conclusion: Liangxue Tongyu Formula ameliorates brain edema in rats after intracerebral hemorrhage by inhibiting MMP-9 expression and activity and up-regulating TIMP-1.