Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats

Tao-yu SUN; Shun-shun FANG; Zi-wei ZHANG; Shuang CHEN; Rong-qian XU; Chun-ying XU; Bin YANG

doi:10.13422/j.cnki.syfjx.20201408

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Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats

Classic Prescriptions | 更新时间：2020-08-11

- Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 15, Pages: 1-7(2020)
- 作者机构：
  
  1.北京中医药大学东直门医院，北京 100700
  2.中国中医科学院西苑医院，北京 100091
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201408
  CLC： R2-0;R22;R285.5;R289
- Revised：18 November 2019，
  
  Published Online：07 May 2020，
  
  Published：05 August 2020
- 稿件说明：
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孙洮玉,方顺顺,张子薇等.加味芎蝎散对咳嗽变异性哮喘大鼠气道平滑肌增殖及MMP-9，TIMP1表达的影响[J].中国实验方剂学杂志,2020,26(15):1-7.

SUN Tao-yu,FANG Shun-shun,ZHANG Zi-wei,et al.Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(15):1-7.
孙洮玉,方顺顺,张子薇等.加味芎蝎散对咳嗽变异性哮喘大鼠气道平滑肌增殖及MMP-9，TIMP1表达的影响[J].中国实验方剂学杂志,2020,26(15):1-7. DOI： 10.13422/j.cnki.syfjx.20201408.

SUN Tao-yu,FANG Shun-shun,ZHANG Zi-wei,et al.Effect of Modified Xiongxiesan on Proliferation of Airway Smooth Muscle Tissues and Expressions of MMP-9 and TIMP1 in CVA Model Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(15):1-7. DOI： 10.13422/j.cnki.syfjx.20201408.

摘要

目的

探讨加味芎蝎散对咳嗽变异性哮喘大鼠气道平滑肌组织增殖以及基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶抑制剂1（TIMP1）表达水平的影响。

方法

雄性SD大鼠48只，随机选取其中8只作为正常组，剩余大鼠随机分成CVA模型组，孟鲁司特钠组（0.4 mg·kg

-1

·d

-1）

，加味芎蝎散组（6 g·kg

-1

·d

-1

），趋化因子受体1/2（CXCR1/2）抑制剂组（G31P，隔日颈部注射0.5 mg·kg

-1

），CXCR1/2抑制剂+加味芎蝎散组，每组8只。腹腔注射卵蛋白（OVA） 2 mg及氢氧化铝［Al（OH）

］ 200 mg，15 d后1%OVA雾化激发建立咳嗽变异性哮喘（CVA）模型，模型建立后各组给予相应的给药处理，正常组及模型组给予10 mL·kg

-1

·d

-1

蒸馏水灌胃。苏木素-伊红（HE）染色后镜下观察肺组织病理形态学变化，测量气道平滑肌层厚度、细胞个数及管壁厚度；免疫组化和蛋白免疫印迹法检测肺支气管平滑肌组织中细胞增殖核抗原（PCNA），MMP-9和TIMP1蛋白表达水平。

结果

与正常组比较，CVA模型组大鼠支气管表现为平滑肌层增生、肥厚，管壁上及周围多量炎性细胞浸润等为主要表现的病理变化，平滑肌层厚度、细胞个数及管壁厚度均增加；与模型组比较，其他药物干预组均有不同程度地减轻。与正常组比较，CVA模型组支气管平滑肌组织中PCNA，MMP-9，TIMP1蛋白明显升高（

0.05），MMP-9/TIMP1蛋白明显升高（

0.05）；与CVA模型组比较，各药物干预组明显降低PCNA，MMP-9，TIMP1蛋白表达及MMP-9/TIMP1蛋白（

0.05）。

结论

加味芎蝎散可以减轻CVA模型大鼠气道平滑肌组织的厚度，可能与抑制CXCR1/2通路，从而降低平滑肌组织的增殖活性以及抑制相关基质金属蛋白酶的表达有关。

Abstract

Objective

To explore the effect of modified Xiongxiesan on the proliferation of airway smooth muscle tissues and the expressions of matrix metalloproteinase-9（MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1） in cough variant asthma （CVA） model rats.

Method

A total 48 male SD rats were randomly divided into the normal control group （8 rats） and model group （40 rats）. CVA model of rats were established through the intraperitoneal administration with 2 mg ovalbumin （OVA） and 100 mg Al（OH）

， and then aerosol inhalation of 1％ OVA 15 days later. The same volume of sterile saline was given to the normal group through the intraperitoneal injection. Then 40 rats in the modeling group were randomly divided into model group， modified Xiongxiesan group （TCM group， 6 g·kg

-1

·d

-1

）， montelukast group （0.4 mg·kg

-1

·d

-1

）， chemokine receptor1/2 （CXCR1/2） inhibitor group （G31P group injected subcutaneously via the neck with a dose of 0.5 mg·kg

-1

every other day）， and CXCR1/2 inhibitor and modified Xiongxiesan group （G31P+TCM group）， with 8 rats in each group. The control group and the model group were orally given distilled water 10 mL·kg

-1

·d

-1

. Then the rats were sacrificed， and lung samples were collected. Histological changes were examined by hematoxylin-eosin（HE）. Basement membrane perimeter （PBM），wall area of bronchial tube （WAt），wall area of bronchial smooth muscle （WAm） and the number of smooth muscle cells （N） were measured using image pro-plus software and standardized based on PBM. The expressions of PCNA， MMP9 and TIMP1 were detected by immunohistochemistry.

Result

Compared with the control group， there were a large number of inflammatory cells infiltration and moderate hyperplasia of smooth muscle area in the model group， which however were alleviated in other groups. The expressions of PCNA and MMP-9，TIMP1 were higher in the model group，which were reduced in other groups significantly.

Conclusion

Modified Xiongxiesan can reduce the thickness of airway smooth muscle tissue in the CVA model rats， which may be correlated with the inhibition of the CXCR1/2 pathway， thereby reducing the proliferative activity of smooth muscle tissue and inhibiting the expression of related matrix metalloproteinases.

关键词

Keywords

references

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