摘要
目的:观察基质金属蛋白酶-2(MMP-2)抑制剂TISAM对实验性自身免疫性心肌炎(EAM)Lewis大鼠模型的治疗效果,并探索可能的治疗机理。方法:口服5 mg/kg TISAM,每日一次,连续14 d治疗EAM Lewis大鼠动物。根据治疗方案不同,分3组,分别为早、中和晚期治疗组(n=20)。治疗结束后,处死动物,心脏取材,进行心肌炎症分级、心肌胶原纤维含量,心肌巨噬细胞和T细胞浸润,MMP-2和MMP-9的mRNA表达,以及明胶酶活性测定。结果:TISAM早期治疗(在模型建立同时开始治疗,持续14 d)无效,中、后期治疗(在模型建立后第7~14天开始治疗,持续14 d)有效。在治疗有效方案中,治疗组与对照组相比,心肌炎症级别下降,心肌间质纤维化级别下降,巨噬细胞和T淋巴细胞浸润数目减少,MMP-2 mRNA表达降低,明胶酶活性降低。结论:MMP-2抑制剂抑制EAM中期的病理发展过程,其机制可能与降低心肌炎症细胞浸润,延缓心肌间质纤维化,从转录水平降低MMP-2 mRNA的表达,同时从蛋白水平降低明胶酶活性表达有关。
Objective: To investigate the inhibitor of matrix metalloproteinase-2 (MMP-2) (2R)-2-[ 5-[4-[ ethyl-methylamino] phenyl [ thiophene-2-sulfonylamino]-3-methylbutyric acid (TISAM) therapeutic effect on experimental autoimmune myocarditis (EAM) in lewis rats. Methods: Treatment protocol of oral administration of 5mg/kg TISAM once a day for 14 days was performed on EAM Lewis rats. EAM lewis rats were divided into 3 groups:treatment in early, middle and later stage respectively( n = 20). After experiment at the designate time peint, the rats were euthanatized and hearts were harvested. Cardiac inflammatory score, fibrosis score and content, and infiltration of macrophages and T lyminflammatory score, fibrosis score and content, and infiltration of macrophages and T lymphocytes, message RNA (mRNA) expression of matrix metalloproteinase (MMP) -2 and MMP-9 and protein activity of gelatinase were determined. Results: TISAM treatment in early phase was invalid (treatment started from the creation of the model), treatment in middle and later phase was effective (treatment started from 7 and 14 day after the creation of the model). Conclusion: Inhibitor of MMP-2 can block ventricular remodeling in middle stage in EAM Lewis rats. The mechanism maybe alleviate the inflammatory cell cardiac infiltration, decrease the mRNA expression of MMP-2 at transcript level and downregulate gelatinase activity at protein level.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2011年第4期452-456,I0015,共6页
Chinese Journal of Applied Physiology
基金
2007年北京市优秀人才培养资助个人项目(20071D1600200391)
2008年北京市科技新星计划(B类)(2008B54)