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[Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis].
Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Feb; 39(2):118-23.ZX

Abstract

OBJECTIVE

To investigate the effects of matrix metalloproteinase-9 (MMP-9) inhibitor minocyclin hydrochloride in Lewis rats with experimental autoimmune myocarditis (EAM).

METHODS

EAM was induced by injection of cardiac C protein emulsified in completed Freund adjuvant in double footpad and intraperitoneal injection of pertussis toxin on 6- to 8-week old Lewis rats. Sixty EAM Lewis rats were divided into 3 groups (early, middle and late intervention groups, n = 20 each: 10 minocyclin treated and 10 control rats). In early intervention group, rats in treatment group received intraperitoneal injection of minocyclin hydrochloride from 1(st) to 21(st) day after immunization; in middle intervention group, rats were treated from 8(th) to 28(th) day after immunization and in late intervention group, rats were treated from 15(th) to 35(th) day after immunization (50 mg/kg body weight, once daily). Control rats received intraperitoneal injection of same volumetric physiological saline at corresponding time periods. At the end of intervention, rats were euthanatized and hearts were harvested. Paraffin sections were used for hematoxylin and eosin stain to determine the inflammatory score, for picrosirius stain to determine fibrosis score and collagen content, and for immunohistological stain to determine macrophages and T lymphocytes. Real time PCR was used to detect mRNA expression of myocardial MMP-2 and MMP-9. Cryostat sections were used for in situ zymography to detect protein activity of gelatinase.

RESULTS

Inflammatory score in cardiac paraffin slides, number of cardiac macrophages and T lymphocytes, cardiac interstitial fibrosis score and content, expression of MMP-2, 9 mRNA and activity of gelatinase in treatment group were all significantly lower than in control group for early and middle intervention groups (inflammatory score: early control group vs. treatment group: 3.03 ± 1.35 vs.1.51 ± 0.36, P < 0.05, middle control group vs. treatment group: 3.75 ± 0.29 vs. 2.11 ± 0.82, P < 0.01; cardiac interstitial fibrosis score, early control group vs. treatment group: 2.75 ± 0.29 vs.1.51 ± 0.35, P < 0.01, middle control group vs. treatment group: 2.50 ± 0.41 vs. 1.61 ± 0.42, P < 0.05; gelatinase, early control group vs. treatment group: 162 367 ± 5095 vs. 62 366 ± 2131, P < 0.01, middle control group vs. treatment group: 184 256 ± 5427 vs. 113 197 ± 4809, P < 0.01) while these parameters were similar between minocyclin-treated and control rats in late intervention group (all P > 0.05).

CONCLUSIONS

MMP-9 plays an important role in the pathogenesis of autoimmune myocarditis. Inhibition of MMP-9 in early and middle stage could significantly attenuate inflammatory responses and myocardial fibrosis in this experimental EAM model.

Authors+Show Affiliations

First Department of Cardiovascular Internal Medicine of South Building, Chinese People's Liberation Army General Hospital, Beijing 100853, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

21426744

Citation

Han, Li-na, et al. "[Effects of Matrix Metalloproteinase-9 Inhibitor in Lewis Rats With Experimental Autoimmune Myocarditis]." Zhonghua Xin Xue Guan Bing Za Zhi, vol. 39, no. 2, 2011, pp. 118-23.
Han LN, Li TL, Zhang YJ, et al. [Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39(2):118-23.
Han, L. N., Li, T. L., Zhang, Y. J., Yang, T. S., Ding, Y., Zhao, X. N., & Guo, S. L. (2011). [Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis]. Zhonghua Xin Xue Guan Bing Za Zhi, 39(2), 118-23.
Han LN, et al. [Effects of Matrix Metalloproteinase-9 Inhibitor in Lewis Rats With Experimental Autoimmune Myocarditis]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39(2):118-23. PubMed PMID: 21426744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis]. AU - Han,Li-na, AU - Li,Tie-ling, AU - Zhang,Ya-jing, AU - Yang,Ting-shu, AU - Ding,Yu, AU - Zhao,Xiao-ning, AU - Guo,Shu-li, PY - 2011/3/24/entrez PY - 2011/3/24/pubmed PY - 2011/12/23/medline SP - 118 EP - 23 JF - Zhonghua xin xue guan bing za zhi JO - Zhonghua Xin Xue Guan Bing Za Zhi VL - 39 IS - 2 N2 - OBJECTIVE: To investigate the effects of matrix metalloproteinase-9 (MMP-9) inhibitor minocyclin hydrochloride in Lewis rats with experimental autoimmune myocarditis (EAM). METHODS: EAM was induced by injection of cardiac C protein emulsified in completed Freund adjuvant in double footpad and intraperitoneal injection of pertussis toxin on 6- to 8-week old Lewis rats. Sixty EAM Lewis rats were divided into 3 groups (early, middle and late intervention groups, n = 20 each: 10 minocyclin treated and 10 control rats). In early intervention group, rats in treatment group received intraperitoneal injection of minocyclin hydrochloride from 1(st) to 21(st) day after immunization; in middle intervention group, rats were treated from 8(th) to 28(th) day after immunization and in late intervention group, rats were treated from 15(th) to 35(th) day after immunization (50 mg/kg body weight, once daily). Control rats received intraperitoneal injection of same volumetric physiological saline at corresponding time periods. At the end of intervention, rats were euthanatized and hearts were harvested. Paraffin sections were used for hematoxylin and eosin stain to determine the inflammatory score, for picrosirius stain to determine fibrosis score and collagen content, and for immunohistological stain to determine macrophages and T lymphocytes. Real time PCR was used to detect mRNA expression of myocardial MMP-2 and MMP-9. Cryostat sections were used for in situ zymography to detect protein activity of gelatinase. RESULTS: Inflammatory score in cardiac paraffin slides, number of cardiac macrophages and T lymphocytes, cardiac interstitial fibrosis score and content, expression of MMP-2, 9 mRNA and activity of gelatinase in treatment group were all significantly lower than in control group for early and middle intervention groups (inflammatory score: early control group vs. treatment group: 3.03 ± 1.35 vs.1.51 ± 0.36, P < 0.05, middle control group vs. treatment group: 3.75 ± 0.29 vs. 2.11 ± 0.82, P < 0.01; cardiac interstitial fibrosis score, early control group vs. treatment group: 2.75 ± 0.29 vs.1.51 ± 0.35, P < 0.01, middle control group vs. treatment group: 2.50 ± 0.41 vs. 1.61 ± 0.42, P < 0.05; gelatinase, early control group vs. treatment group: 162 367 ± 5095 vs. 62 366 ± 2131, P < 0.01, middle control group vs. treatment group: 184 256 ± 5427 vs. 113 197 ± 4809, P < 0.01) while these parameters were similar between minocyclin-treated and control rats in late intervention group (all P > 0.05). CONCLUSIONS: MMP-9 plays an important role in the pathogenesis of autoimmune myocarditis. Inhibition of MMP-9 in early and middle stage could significantly attenuate inflammatory responses and myocardial fibrosis in this experimental EAM model. SN - 0253-3758 UR - https://www.unboundmedicine.com/medline/citation/21426744/[Effects_of_matrix_metalloproteinase_9_inhibitor_in_Lewis_rats_with_experimental_autoimmune_myocarditis]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0253-3758&amp;year=2011&amp;vol=39&amp;issue=2&amp;fpage=118 DB - PRIME DP - Unbound Medicine ER -