Chinese Journal of Tissue Engineering Research ›› 2015, Vol. 19 ›› Issue (50): 8120-8125.doi: 10.3969/j.issn.2095-4344.2015.50.015

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Effect of buyang huanwu decoction combined with bone marrow mesenchymal stem cell transplantation on cerebral ischemia-reperfusion injury

Zhang Yun-ke1, 2, Song Jun-ying1, Zhang Zhen-qiang1   

  1. Zhang Yun-ke, M.D., Chief physician, Professor, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, Henan Province, China; First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • Received:2015-10-16 Online:2015-12-03 Published:2015-12-03
  • Contact: Zhang Zhen-qiang, M.D., Professor, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • About author:Zhang Yun-ke, M.D., Chief physician, Professor, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, Henan Province, China; First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81072799/H2708

Abstract:

BACKGROUND: When acute cerebral ischemia attacks, matrix metalloproteinases (MMPs) lead to the occurrence of cerebral edema through degrading the extracellular matrix, breaking the close connection between endothelial cells, increasing the permeability of capillaries, and destroying the blood brain barrier.
OBJECTIVE: From the aspects of MMPs and extracellular matrix, to discuss the therapeutic effects of buyang huanwu decoction combined with bone marrow mesenchymal stem cell (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) and buyang 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 collected 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, especially the levels of MMP-9 (P < 0.05). Compared with the BMSCs group, the levels of MMP-2 and MMP-9 in serum as well 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 the buyang huanwu decoction can be mutually cooperated with TIMP-1 to inhibit the degradation of extracellular matrix induced by MMP-2 and MMP- 9, repair the damaged blood brain barrier, prevent and cure cerebral edema after ischemia.

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