凉血通瘀方对脑出血大鼠脑水肿及基质金属蛋白酶9和金属蛋白酶组织抑制剂1表达的影响

doi:10.3736/jcim20100408

Abstract

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

Chun-yan He , Jian-hua Huang, Wen-jian Wang, Miao-wen Jin, Fang Ye, Hai-tao Wu, Wei-hua Chen, Mian-hua Wu. 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. Journal of Chinese Integrative Medicine, 2010, 8(4): 347-351.

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URL: http://www.jcimjournal.com/EN/10.3736/jcim20100408

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References 15

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Group	n	Brain water content
Group	n	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^△△

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^△△

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^**△△

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

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