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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

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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【作者】 何春燕黄建华王文健金妙文叶放吴海涛陈伟华吴勉华

【Author】 Chun-yan HE~1,Jian-hua HUANG~2,Wen-jian WANG~2,Miao-wen JIN~3,Fang YE~3,Hai-tao WU~4,Wei-hua CHEN~2,Mian-hua WU~3 1.Postdoctoral Center of Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu Province,China 2.Institute of Chinese Integrative Medicine,Fudan University,Shanghai 200040,China 3.Department of Traditional Chinese Internal Medicine,the First Medical College,Nanjing University of Chinese Medicine, Nanjing 210029,Jiangsu Province,China 4.Cytobiology Laboratory,Preclinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu Province,China

【机构】 南京中医药大学中医学博士后流动站复旦大学中西医结合研究所南京中医药大学第一临床医学院中医内科教研室南京中医药大学基础医学院细胞生物学实验室

【摘要】 目的:探讨中药凉血通瘀方对脑出血大鼠脑水肿的作用及其机制。方法:采用自体血纹状体注射方法制备大鼠脑出血模型。实验大鼠分为假手术组、模型组和凉血通瘀方组。凉血通瘀方组给予凉血通瘀煎剂灌胃,余两组给予生理盐水灌胃,每日1次。脑出血后24、48、72和120 h观察大鼠脑水肿情况,明胶酶谱法检测脑血肿周围组织内基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)活性,荧光定量实时聚合酶链式反应法检测MMP-9和基质金属蛋白酶组织抑制剂1(tissueinhibitor ofmetalloproteinase-1,TIMP-1)的表达水平。结果:凉血通瘀方组大鼠脑水肿程度在各时间点均显著低于模型组(P<0.01),仅在72 h其脑组织含水量高于假手术组(P<0.01)。与模型组相比,凉血通瘀方组的MMP-9酶原水平及活性均显著降低,其mRNA水平亦在脑出血后48、72、120 h低于模型组(P<0.01),而TIMP-1 mRNA水平在各时间点均显著升高(P<0.01)。结论:凉血通瘀方可能通过上调TIMP-1表达来抑制MMP-9水平,从而减轻脑出血大鼠脑水肿。

【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.

【基金】 国家重点基础研究发展计划(973计划)资助项目(No.2006CB504807);中国博士后科学基金资助项目(No.20080441068);南京中医药大学中医内科学重点学科资助项目(No.zynk006)
  • 【文献出处】 中西医结合学报 ,Journal of Chinese Integrative Medicine , 编辑部邮箱 ,2010年04期
  • 【分类号】R285.5
  • 【被引频次】19
  • 【下载频次】290
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