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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (4): 347-351.doi: 10.3736/jcim20100408

• Original Experimental Research • Previous Articles     Next Articles

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

 Chun-yan Hea, Jian-hua Huangb, Wen-jian Wangb, Miao-wen Jinc, Fang Yec, Hai-tao Wud, Wei-hua Chenb, Mian-hua Wuc    

  1. a Postdoctoral Center of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
    b Institute of Chinese Integrative Medicine, Fudan University, Shanghai 200040, China
    c Department of Traditional Chinese Internal Medicine, the First Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
    d Cytobiology Laboratory, Preclinical Medical College,Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
  • Received:2010-02-05 Accepted:2010-03-05 Online:2010-04-20 Published:2010-04-15
  • Contact: Mian-hua Wu E-mail:xueping226@yahoo.cn

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.

Key words: Intracerebral hemorrhage, Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinase-1, Compound (TCD), Rats

Table 1

Brain water content in the three groups ($\bar{x}$±s, %)"

Group
n Brain water content
24 h 48 h 72 h 120 h
SO 6 68.67±2.16 68.33±2.58 68.50±1.87 67.17±2.32
ICH 6 74.17±2.48** 80.33±1.86** 82.00±2.83** 74.00±1.79**
LXTYF 6 72.50±2.88 72.17±3.06△△ 74.50±1.87**△△ 67.50±2.17△△

Figure 1

MMP-9 activities and pro-MMP-9 levels in three groups"

Table 2

MMP-9 activities and pro-MMP levels in three groups ($\bar{x}$±s)"

Group n Time (h) Pro-MMP-9 Act-MMP-9
SO 6 72 6 528.83±820.11 6 463.83±606.05
ICH
6 24 3 106.17±595.68** 3 040.33±684.79**
6 48 1 248.33±374.45** 1 188.33±329.18**
6 72 398.33±318.28** 380.00±286.17**
6 120 1 917.00±535.15** 1 890.33±478.75**
LXTYF
6 24 5 013.67±651.04**△△ 4 973.67±608.17**△△
6 48 3 571.67±429.46**△△ 3 605.00±442.23**△△
6 72 2 206.50±381.89**△△ 2 154.83±379.72**△△
6 120 6 134.00±900.03△△ 6 070.67±896.62△△

Table 3

MMP-9 and TIMP-1 mRNA expressions in three groups ($\bar{x}$±s)"

Group n Time (h) MMP-9 mRNA/GAPDH mRNA TIMP-1 mRNA/GAPDH mRNA
SO
6 24 0.06±0.01 0.08±0.01
6 48 0.07±0.01 0.09±0.01
6 72 0.06±0.01 0.09±0.01
6 120 0.07±0.01 0.09±0.03
ICH
6 24 0.15±0.03** 0.09±0.01
6 48 0.30±0.06** 0.09±0.01
6 72 0.75±0.17** 0.13±0.03*
6 120 0.49±0.12** 0.12±0.03
LXTYF
6 24 0.12±0.02** 0.14±0.01**△△
6 48 0.18±0.04**△△ 0.22±0.02**△△
6 72 0.27±0.07*△△ 0.30±0.03**△△
6 120 0.13±0.02△△ 0.26±0.06**△△
[1] Qureshi AI, Mendelow AD, Hanley DF . Intracerebral hemorrhage[J]. Lancet, 2009,373(9675):1632-1644
doi: 10.1016/S0140-6736(09)60371-8
[2] Abilleira S, Montaner J, Molina CA, Monasterio J, Castillo J, Alvarez-Sabín J . Matrix metalloproteinase concentration after spontaneous intracerebral hemorrhage[J]. J Neurosurg, 2003,99(1):65-70
doi: 10.3171/jns.2003.99.1.0065
[3] Jin MW, Zhou ZY, Fan Y, Wu MH, Zhou XP, Wang ZY, Wang H . Clinical study of Liangxue Tongyu oral solution in treatment of patients with hemorrhagic stroke at acute stage and traditional Chinese medical syndrome of stagnant heat and obstruction of orifices[J]. Zhongguo Zhong Xi Yi Jie He Ji Jiu Za Zhi, 2007,14(6):323-327
金妙文, 周仲瑛, 樊蓥, 吴勉华, 周学平, 王志英, 汪红 . 凉血通瘀口服液治疗出血性中风病急性期瘀热阻窍证的临床研究[J]. 中国中西医结合急救杂志, 2007,14(6):323-327
[4] Hua Y, Schallert T, Keep RF, Wu J, Hoff JT, Xi G . Behavioral tests after intracerebral hemorrhage in the rat[J]. Stroke, 2002,33(10):2478-2484
doi: 10.1161/01.STR.0000032302.91894.0F
[5] Zausinger S, Hungerhuber E, Baethmann A, Reulen H, Schmid-Elsaesser R . Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms[J]. Brain Res, 2000,863(1-2):94-105
doi: 10.1016/S0006-8993(00)02100-4
[6] Yan J, Chen C, Hu Q, Yang X, Lei J, Yang L, Wang K, Qin L, Huang H, Zhou C . The role of p53 in brain edema after 24 h of experimental subarachnoid hemorrhage in a rat model[J]. Exp Neurol, 2008,214(1):37-46
doi: 10.1016/j.expneurol.2008.07.006
[7] Xi G, Keep RF, Hoff JT . Mechanisms of brain injury after intracerebral hemorrhage[J]. Lancet Neurol, 2006,5(1):53-63
doi: 10.1016/S1474-4422(05)70283-0
[8] Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH . Role of matrix metalloproteinases in delayed cortical responses after stroke[J]. Nat Med, 2006,12(4):441-445
doi: 10.1038/nm1387
[9] Rosell A, Ortega-Aznar A, Alvarez-Sabín J , Fernández-Cadenas I, Ribó M, Molina CA, Lo EH, Montaner J . Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke[J]. Stroke, 2006,37(5):1399-1406
doi: 10.1161/01.STR.0000223001.06264.af
[10] Rosell A, Cuadrado E, Ortega-Aznar A , Hernández-Guillamon M, Lo EH, Montaner J .MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type Ⅳ collagen degradation during hemorrhagic transformation after human ischemic stroke[J]. Stroke, 2008,39(4):1121-1126
doi: 10.1161/STROKEAHA.107.500868
[11] Rosell A, Lo EH . Multiphasic roles for matrix metalloproteinases after stroke[J]. Curr Opin Pharmocol, 2008,8(1):82-89
doi: 10.1016/j.coph.2007.12.001
[12] Fu X, Parks WC, Heinecke JW . Activation and silencing of matrix metalloproteinases[J]. Semin Cell Dev Biol, 2008,19(1):2-13
doi: 10.1016/j.semcdb.2007.06.005
[13] Lambert E, Dassé E, Haye B, Petitfrère E . TIMPs as multifacial proteins[J]. Crit Rev Oncol Hematol, 2004,49(3):187-198
doi: 10.1016/j.critrevonc.2003.09.008
[14] Overall CM, Blobel CP . In search of partners: linking extracellular proteases to substrates[J]. Nat Rev Mol Cell Biol, 2007,8(3):245-257
[15] Rosenberg GA, Navratil M . Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat[J]. Neurology, 1997,48(4):921-926
doi: 10.1212/WNL.48.4.921
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