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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (8): 810-816.doi: 10.3736/jcim20080808

• Original Experimental Research • Previous Articles     Next Articles

Effects of rhubarb aglycone on matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell transplantation

Jian-sheng Li1(), Jing-xia Liu1, Jie Sun1, Yue-wu Zhao2, Jing Su1, Ning Li1, Xiao-yan Guo1   

  1. 1. Institute of Geriatrics, Henan College of Traditional Chinese Medicine, Zhengzhou, Henan Province 450008, China
    2. Department of Pathology, Henan Province People's Hospital, Zhengzhou, Henan Province 450003, China
  • Received:2007-11-22 Online:2008-08-20 Published:2008-08-15

Objective: To observe the effects of rhubarb aglycone on pathological changes and activity of matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell (BMSC) transplantation, and to explore the action mechanisms of rhubarb aglycone in protecting against brain micrangium injury in rats.
Methods: The BMSCs were purified and amplified by methods of adherence and selection in vitro. One hundred and ninety rats were randomly divided into sham-operated group, untreated group, rhubarb aglycone group, BMSC transplantation group (abbreviated as transplantation group) and BMSCs combined with rhubarb aglycone group (abbreviated as combination group). Middle cerebral artery occlusion (MCAO) model was duplicated with nylon thread. Rats of transplantation and combination group were transplanted with BMSCs via carotid artery after 24-hour reperfusion. Rhubarb aglycone was used by intragastric administration in the rhubarb aglycone group and the combination group. The brain samples were taken at 7, 14 and 28 days after transplantation. Brain micrangium pathological changes were observed by light microscope, and immunohistochemical method was used to determine the expressions of immunoglobulin G (IgG), type Ⅳ collagen (col Ⅳ), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1).
Results: Comparison with the normal control group revealed that brain micrangium in rats in the untreated group was obviously mutilated and damaged, the expression of IgG and MMP-9 increased, and showed a progressively enhanced tendency following the prolongation of reperfusion, while the expressions of col Ⅳ and TIMP-1 were decreased, and TIMP-1 showed a attenuated tendency following the prolongation of reperfusion. Comparing with the untreated group, the improvements of brain micrangium structure in the rhubarb aglycone group (7 days after transplantation), the transplantation group (14 and 28 days after transplantation) and the combination group were significant; expression of IgG and activity of MMP-9 were decreased, while expressions of Col Ⅳ and TIMP-1 were increased in the rhubarb aglycone group and the combination group at each time point. The brain micrangium was integral and the expression of Col Ⅳ was enhanced in combination group (7 days after transplantation) as compared with those in transplantation group. MMP-9 activity in combination group (14 days after transplantation) was lower than that in the rhubarb aglycone group (14 days after transplantation), while expression of TIMP-1 in combination group also increased significantly as compared with that in transplantation group (28 days after transplantation).
Conclusion: Rhubarb aglycone can decrease the degradation of basal lamina Col Ⅳ and the permeability of brain micrangium in cerebral ischemic rats with BMSC transplantation, and its mechanisms may be related to regulating the balance of MMP-9, especially by increasing the expression of TIMP-1.

Key words: cerebral ischemia, rats, rhubarb aglycone, bone marrow mesenchymal stem cells, blood brain barrier, matrix metalloproteinase

CLC Number: 

  • R285.5

Figure 1

Pathological changes of brain micrangium in rats in different groups at the twenty-eighth day (HE staining, ×200) A: Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Table 1

Expressions of IgG, ColⅣ, TIMP-1 and activity of MMP-9 in brain of rats in different groups (x±s, IOD×10-2)"

Group n IgG ColⅣ MMP-9 TIMP-1
Sham-operated 6 13.85±2.08 42.71±8.86 24.32±6.29 22.25±4.26
Untreated
7 days 7 34.87±6.14 23.56±3.44 62.65±7.39 20.47±4.75
14 days 6 49.70±11.49□□ 15.79±2.46 64.43±9.37 18.44±2.19
28 days 6 53.00±7.57**□□ 15.59±1.83** 82.76±13.24**□□■■ 16.84±2.00
Rhubarb aglycone
7 days 7 20.92±8.74△△ 40.86±5.19△△ 48.56±12.79 46.25±11.13△△☆☆
14 days 7 21.40±4.22△△ 45.24±4.92△△ 51.90±24.38△☆ 24.91±3.70△△☆☆□□
28 days 6 32.32±8.98△△□■■ 39.18±7.48△△ 42.22±8.89△△ 30.64±5.01△△□□
Transplantation
7 days 7 28.86±3.91▲▲ 27.71±4.70▲▲☆☆ 50.91±8.16 35.87±5.72△△▲▲
14 days 6 20.08±5.91△△□ 32.54±4.30△△▲☆☆ 31.99±5.98△△▲▲□□ 42.37±8.93△△▲▲
28 days 6 22.92±4.93△△▲ 34.33±5.09△△☆ 39.18±10.79△△ 29.61±3.13△△□☆
Combination
7 days 7 25.20±8.70△△ 44.48±14.38△△ 48.95±20.45 35.88±6.87△△
14 days 6 27.68±10.72△△ 49.52±7.35△△ 32.48±7.37△△□□ 35.19±13.31△△
28 days 7 26.00±1.51△△ 45.27±8.13△△ 36.19±5.57△△□ 36.39±5.08△△

Figure 2

Expression of IgG in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 3

Expression of Col Ⅳ in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 4

Expression of MMP-9 in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 5

Expression of TIMP-1 in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

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