化痰通络方对急性脑梗死大鼠rt-PA溶栓后MMP-9转录活化途径中AP-1与NF-B基因表达的影响

周震; 张玉莲; 张琳琳; 韩文文; 宋宛珊; 王凯

doi:10.13422/j.cnki.syfjx.2014150122

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化痰通络方对急性脑梗死大鼠rt-PA溶栓后MMP-9转录活化途径中AP-1与NF-B基因表达的影响

药理 | 更新时间：2024-01-04

- 化痰通络方对急性脑梗死大鼠rt-PA溶栓后MMP-9转录活化途径中AP-1与NF-B基因表达的影响
- Effect of Huatan Tongluo Formulae on Expression of AP-1 and NF-B on Gene Transcription Activation Pathway of MMP-9 in Rat Cortex Accepted Thrombolysis Pherapy after Acute Cerebral Infarction
- 中国实验方剂学杂志 2014年20卷第15期页码：122-126
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金项目（81072796）;天津市应用基础及前沿技术研究计划（12JZDJC25300）;天津市教委“十二五”创新团队培养计划项目（TD12-5035）
- DOI：10.13422/j.cnki.syfjx.2014150122
  中图分类号： R285.5
- 纸质出版日期：2014
- 稿件说明：
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周震, 张玉莲, 张琳琳, 等. 化痰通络方对急性脑梗死大鼠rt-PA溶栓后MMP-9转录活化途径中AP-1与NF-B基因表达的影响[J]. 中国实验方剂学杂志, 2014,20(15):122-126.

ZHOU Zhen, ZHANG Yu-lian, ZHANG Lin-lin, et al. Effect of Huatan Tongluo Formulae on Expression of AP-1 and NF-B on Gene Transcription Activation Pathway of MMP-9 in Rat Cortex Accepted Thrombolysis Pherapy after Acute Cerebral Infarction[J]. Chinese journal of experimental traditional medical formulae, 2014, 20(15): 122-126.
周震, 张玉莲, 张琳琳, 等. 化痰通络方对急性脑梗死大鼠rt-PA溶栓后MMP-9转录活化途径中AP-1与NF-B基因表达的影响[J]. 中国实验方剂学杂志, 2014,20(15):122-126. DOI： 10.13422/j.cnki.syfjx.2014150122.

ZHOU Zhen, ZHANG Yu-lian, ZHANG Lin-lin, et al. Effect of Huatan Tongluo Formulae on Expression of AP-1 and NF-B on Gene Transcription Activation Pathway of MMP-9 in Rat Cortex Accepted Thrombolysis Pherapy after Acute Cerebral Infarction[J]. Chinese journal of experimental traditional medical formulae, 2014, 20(15): 122-126. DOI： 10.13422/j.cnki.syfjx.2014150122.

摘要

目的：观察化痰通络方对急性脑梗死大鼠重组组织纤溶酶原激活剂（rt-PA）溶栓后基质金属蛋白酶-9（MMP-9）及其基因转录活化途径中激活蛋白-1（AP-1）与核因子κB（NF-κB）基因表达的影响。方法：选择240只健康SD大鼠，随机分为假手术组、模型组、rt-PA组、化痰通络方联合rt-PA组（简称中药组，中药组分低、中、高剂量组），采用自身栓子法制备大鼠大脑中动脉栓塞模型（MCAO），rt-PA组与中药组分别给予尾静脉注入rt-PA（5.67 mg·kg-1）及联合3种不同剂量化痰通络方中药（3.6，7.2，14.4 g·kg-1）干预，每日2次。于相应时间点采用Western blot检测各组大鼠大脑皮质梗死区组织中MMP-9蛋白的表达，采用逆转录聚合酶链反应（Real Time PCR）方法检测MMP-9基因转录活化途径中AP-1与NF-κB基因的表达。结果：Western blot结果显示：模型组内各个时相大鼠MMP-9含量较假手术组均显著增加（P<0.05）；加入中药干预后，MMP-9蛋白表达明显减少，其中以中、高剂量效果显著（P<0.05）。Real Time PCR结果显示：与假手术组比较，模型组AP-1与NF-κB基因相对表达量均明显增加（P<0.05）；与模型组相比，加入中药干预后，2种基因均有所降低，以中药中、高剂量作用明显，同一时相内与rt-PA组相比，在6 h和24 h时，中药高剂量作用优于rt-PA，在72 h和7 d时，中药中剂量作用优于rt-PA。结论：化痰通络方可通过调控MMP-9上游基因转录途径中AP-1与NF-κB基因的表达，部分抑制其活化程度，进而保护血脑屏障完整性，从而更好的防治急性脑梗死溶栓后转化出血的发生与发展。

Abstract

Objective: To observe the effect of Huatan Tongluo formulae on express of motrix metallo proteinase-9(MMP-9) and activator protein-1(AP-1) and nuclear factor kappa B(NF-κB) on gene transcription activation pathway in rat cortex accepted thrombolysis therapy after the acute cerebral infarction. Method: Two handred and forty healthy male SD rats were randomly divided into sham group

model group

recombinant tissue plasminogen activator(rt-PA) group

rt-PA-Huatan Tongluo group (Chinese medicine group for short)

Chinese medicine group were divided high dose group

middle dose group and low dose group

drug respectively as:3.6

7.2

14.4 g·kg-1)

each group was divided into four time phases:6

72 h

7 days. In the corresponding time points prepares the middle cerebral artery occulation(MCAO) rat model

the rats in rt-PA group were injected rt-PA(5.67 mg·kg-1)

and those of Chinese medicine group were given rt-PA and three different doses of Huatan Tongluo formulae

2 times a day. Then respectively observe the protein expression of MMP-9 by Western blot observe the gene expression of AP-1 and NF-κB on gene transcription activation pathway by RT PCR. Result: The result of Western blot showed:compared with sham group

the expression of MMP-9 increased significantly(P<0.05)

compared with model group in the same time phases

the expression of MMP-9 decreased in Chinese medicine group

especially in high dose group and middle dose group. RT PCR showed that compared with sham group

the expression of AP-1 and NF-κB increased significantly in model group (P<0.05)

the expression of two genes in Chinese medicine group

especially in high dose group and middle dose group.Compared with rt-PA group

the expression of AP-1 and NF-κB decreased in high dose group at 6

24 h and in middle dose group at 72 h and 3 d. Conclusion: Huatan Tongluo can inhibit the activation of MMP-9

protect the blood brain barrier by regulating AP-1 and NF-κB on gene transcription activation pathway of MMP-9.

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