摘要
目的探讨基质金属蛋白酶-3(MMP-3)及金属蛋白酶组织抑制因子-1(TI MP-1)在病毒性心肌炎(VM)小鼠中的作用及肾素-血管紧张素系统抑制剂(RASI)的治疗效果。方法100只Balb/c小鼠随机分为对照组(A组)、模型组(B组)、假干预组(C组)、福辛普利组(D组)和缬沙坦组(E组)5组,每组20只。B^E组小鼠腹腔接种0.1ml的柯萨奇病毒B3(CVB3)悬液建立VM模型,A组腹腔注射不含CVB3的0.1ml Hep-2细胞冻溶液作对照组。C组、D组及E组于注射CVB324h后分别予生理盐水、福辛普利、缬沙坦灌胃,第14天处死小鼠,心脏切片HE染色计算病理积分,氯氨T法测定心肌胶原含量,RT-PCR法检测心肌MMP-3、TI MP-1mRNA的表达。结果与A组比较,B组、C组心肌MMP-3表达明显上调,TI MP-1表达明显下调,心肌胶原含量显著增高(P均<0.05);与B组比较,D组、E组心肌MMP-3表达明显下调,TI MP-1表达明显上调,心肌胶原含量显著减少(P均<0.05)。结论MMP-3/TI MP-1参与VM小鼠的心肌病理过程,可能是导致心肌胶原重构的重要因素之一。福辛普利及缬沙坦能明显下调MMP-3的表达、上调TI MP-1的表达,逆转心肌胶原重构。
Objectives To explore the role of myocardial matrix metalloproteinase-3（MMP-3）,tissue inhibitor of metalloproteinase-1（TIMP-1） in mice with viral myocarditis （VM） and to evaluate the effects of rennin-angiotensin-system inhibitor（RASI） . Methods A hundred Balb/c mice were divided into five groups randomly ： group A（con trol ）, B （model）, C （ sham in terven tion）, D （fosinopril） and E （valsar tan）, with 20 mice in each group. Mice in infected group（B--E, n = 80） were inoculated intraperitoneally with 0.1 ml of Coxackievirus B3（CVB3 Nancy strain） .Group A（control, n = 20） was inoculated intraperitoneally with 0.1 ml of Hep-2＇s solution without Coxackievirus B3. After 24 h of inoculation, group C, D and E were treated with normal saline, fosinopril 15 mg/（kg ·d） and valsartan 30 mg/（kg · d） respectively. All mice were fed routinely and sacrificed on day 14. Histological cross sections of heart were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Myocardial collagen amount was measured by determination of hydroxyproline quantification,and the mRNA expression of MMP-3 and TIMP-1 was detected with reverse transcription-polymerase chain reaction （RT-PCR） . Results The mRNA expression of MMP-3 in group B and C was upregulated remarkably in comparison with those in group A（P〈 0.05） . The myocardial collagen amount in group B and C increased significantly in comparison with that in control group. The mRNA expression of MMP-3 in group D and E was downregulated significantly and the mRNA expression of TIMP-1 was upregulated remarkably in comparison with that in group B（P〈 0.05）. Conclusions The changes of myocardial MMP-3 and TIMP-1 were associated with myocardial pathologic lesion of VM, and may contributes to myocardial collagen remodeling in myocarditis mice. The mRNA expression of MMP-3 was downregulated and the mRNA expression of TIMP-1 was upregulated significantly by fusinopril and valsartan, thus reversed the myocardial collagen remodeling.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2005年第10期727-730,共4页
Journal of Clinical Pediatrics
基金
广西科学基金资助(编号:桂科基0448048)
