[an error occurred while processing this directive]

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

RichHTML

1

PDF (PC)

87

Like

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
[1] Na Wu , Lu Song , Xin-xin Yang, Jiang-lei Wei , Zhen-guo Liu. Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1018-1024.
[2] Lawrence A. Olatunji, Taofeek O. Usman, Joseph O. Adebayo, Victoria A. Olatunji . Effects of aqueous extract of Hibiscus sabdariffa on renal Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in Wistar rats. Journal of Chinese Integrative Medicine, 2012, 10(9): 1049-1055.
[3] Dhirender Kaushik, Ajay Kumar, Pawan Kaushik, Avatar C. Rana. Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. Journal of Chinese Integrative Medicine, 2012, 10(9): 1056-1060.
[4] Chan Chen, Chang-xun Chen, Xi-min Wu, Rui Wang, Yi-ming Li. Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms. Journal of Chinese Integrative Medicine, 2012, 10(9): 1009-1017.
[5] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[6] Karuna A. Talpate, Uma A. Bhosale, Mandar R. Zambare. Clitorea ternatea, a herb from Indian folklore, improves streptozotocin-induced diabetes and diabetes-induced cognitive decline in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 939-947.
[7] Samuel Joshua Pragasam, Vachana Murunikara, Evan Prince Sabina, Mahaboobkhan Rasool. Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced arthritis in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 932-938.
[8] Zi-hui Li, Jian Wang, Rong-lin Cai, You-wen Wang, Jian-peng Hu. Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency. Journal of Chinese Integrative Medicine, 2012, 10(8): 918-924.
[9] Meng Li, Ling Hu, Rong-lin Cai, Zi-jian Wu, Ke-ming Wang. Effects of electro-acupuncture at PC6 and BL15 on nerve electrical activity in spinal dorsal root and norepinephrine and dopamine contents in paraventricular nucleus of hypothalamus in rats with acute myocardial ischemia. Journal of Chinese Integrative Medicine, 2012, 10(8): 874-879.
[10] Hong Wang , Jing-tian Ou , Xin Zhao , Ying Guoz , Hao-ping Mao. Vasodilator effect of oroxylin A on thoracic aorta isolated from rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 880-885.
[11] Yong Zhang, Xiao-wen Sun, Jian-hua Xu, Hai Lu, Zhong-ze Fan, Jue Sun, Xiao-xiao Zhang. Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on pharmacokinetics of oxaliplatin in colon cancer cells. Journal of Chinese Integrative Medicine, 2012, 10(8): 901-910.
[12] Xin-min Li, Hui Chen, Yan-yan Ren, Yan-li Lu. Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance-associated protein 1 expression in hippocampus and cortex of rats with lithium-pilocarpine-induced epilepsy. Journal of Chinese Integrative Medicine, 2012, 10(8): 911-917.
[13] C. Mouli Kalla, Vijaya Tartte, Dattatreya Rao Sirpurkar. Effectiveness of flavonoid-rich leaf extract of Acalypha indica in reversing experimental myocardial ischemia: biochemical and histopathological evidence. Journal of Chinese Integrative Medicine, 2012, 10(7): 784-792.
[14] Feng Xin-ying, Zhu Min, Zhang Qi-qi, Chen Yi-ping, Li Wen-wei. Selective protection of nigral dopaminergic neurons by echinacoside in a rat model of Parkinson disease induced by rotenone. Journal of Chinese Integrative Medicine, 2012, 10(7): 777-783.
[15] Chuan Chen, Hui-ying Chi, Zhi-hua Yu, Jiu-lin Chen . Effects of Chinese herbal medicine Shoushen Granule on telomere length and telomerase activity of peripheral white blood cells and vascular cells in rats with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(6): 667-673.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278
[an error occurred while processing this directive]