Effect ofbuyang huanwu decoction combined with bone marrow mesenchymal stem cell transplantation on cerebral ischemia-reperfusion injury / 中国组织工程研究

ABSTRACT

BACKGROUND:When acute cerebral ischemia attacks, matrix metaloproteinases (MMPs) lead to the occurrence of cerebral edema through degrading the extracelular matrix, breaking the close connection between endothelial cels, increasing the permeability of capilaries, and destroying the blood brain barrier. OBJECTIVE: From the aspects of MMPs and extracelular matrix, to discuss the therapeutic effects ofbuyang huanwu decoction combined with bone marrow mesenchymal stem cel (BMSCs) transplantation on cerebral ischemia-reperfusion injury. METHODS:A total of 96 Sprague-Dawley rats were randomly divided into model group, tissue inhibitor of MMPs-1 (TIMP-1) group, TIMP-1+BMSCs group (BMSCs group) andbuyang huanwu decoction+BMSCs+TIMP-1 group (combined group that was divided into four subgroups, 12-, 24-, 36-, 48-hour groups). Rat models of cerebral ischemia-reperfusion were constructed, and TIMP-1 and BMSCs were injected to the brain of rats by a microinjector in a stereotaxic apparatus. Rats in the combined group were given buyang huanwu decoction (10 mL/kg), and rats in the other groups were given the same volume of normal saline at 7 days before surgery. After 10 days of administration, serum samples and brain tissues were colected to determine MMP-2 and MMP-9 levels using ELISA and to detect MMP-9 activity using gelatinases spectrometry method. RESULTS AND CONCLUSION:Compared with the model group, the levels of MMP-2 and MMP-9 in the serum and MMP-9 activity in the brain were decreased in the other groups to different extents, especialy the levels of MMP-9 (P < 0.05). Compared with the BMSCs group, the levels of MMP-2 and MMP-9 in serum as wel as activities of MMP-9 and pro-MMP-9 in the brain were decreased significantly in the combined group at 36 and 48 hours after treatment (P< 0.01). The results show that thebuyang huanwu decoction can be mutualy cooperated with TIMP-1 to inhibit the degradation of extracelular matrix induced by MMP-2 and MMP- 9, repair the damaged blood brain barrier, prevent and cure cerebral edema after ischemia.