伊伐布雷定对病毒性心肌炎小鼠心肌炎症细胞因子的影响  

Effects of Ivabradine on the expression of inflammatory cytokines in a murine model of coxsackievir-us B3-induced viral myocarditis

作　　者：周娜丹[1,2] 张腾[1] 李岳春[1] 革丽莎[3] 

机构地区：[1]温州医科大学附属第二医院,325027 [2]温州医科大学附属乐清医院心内科,325600 [3]温州医科大学儿科

出　　处：《中华微生物学和免疫学杂志》2013年第10期734-739,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金（81200165）;浙江省自然科学基金（Y2100551）;温州市科技局基金（Y20130038）

摘　　要：目的：对比研究单纯降低心率药物伊伐布雷定和β受体阻断剂卡维地洛对柯萨奇B3（ CVB3）病毒性心肌炎小鼠的作用，探讨伊伐布雷定和卡维地洛对急性病毒性心肌炎小鼠心肌炎症因子的影响。方法随机将150只雄性BALB/c小鼠分为4组：空白对照组（ n＝30），心肌炎组（ n＝40），伊伐布雷定组（n＝40），卡维地洛组（n＝40）。后3组经腹腔接种CVB3诱发急性病毒性心肌炎，空白组腹腔注射磷酸缓冲液，接种当天记为第0天，24 h后伊伐布雷定组和卡维地洛组每日灌胃分别给予伊伐布雷定10 mg/kg、卡维地洛10 mg/kg，空白组给予磷酸盐缓冲液灌胃，直至第14天末。于接种第4天、7天、14天随机从各组抽取小鼠测心率后处死取心脏。小鼠心肌病理切片HE染色观察炎症病理改变，半定量RT-PCR检测心肌病毒RNA，半定量RT-PCR和ELISA法检测心肌组织MCP-1、IL-6及TNF-αmRNA和蛋白水平。结果与心肌炎组比较，7 d、14 d伊伐布雷定和卡维地洛组心肌病理损伤明显减轻。与空白组比较，心肌炎组在第4天、7天心肌MCP-1、IL-6及TNF-α的转录水平明显上调，与心肌炎组比较，第4天伊伐布雷定组和卡维地洛组心肌TNF-α转录均下调，第7天两者IL-6的转录下调，仅伊伐布雷定组MCP-1转录下调。蛋白水平改变和mRNA基本一致。结论伊伐布雷定具有和卡维地洛相似地减轻心肌炎小鼠的心肌炎症损害的作用，其显著下调TNF-α和IL-6 mRNA及蛋白水平，效果与卡维地洛相似，此外，伊伐布雷定还能显著下调MCP-1的mRNA和蛋白水平。in mice with coxsackievirus B3 （CVB3）-induced viral myocarditis through a comparative study with Carve-dilol.Methods 150 BALB/c male mice were divided into four groups including control group （n=30）, myocarditis group （n=40）, Ivabradine treatment group （n=40） and Carvedilol treatment group （n=40）. Viral myocarditis was induced by intraperitoneal injection of CVB 3 in experimental mice , while mice in the control group were injected with PBS accordingly .The mice in four groups were respectively administered with PBS, PBS, Ivabradine and Carvedilol after 24 h of infection for 14 consecutive days .Heart specimens were collected from 8 mice of each group on days 4, 7 and 14 after measuring their heart rates .The patho-logical changes in heart tissues were observed through hematoxylin e-osin staining .Semi-quantitative RT-PCR and ELISA were performed to detect the expressions of MCP -1, IL-6 and TNF-αat mRNA and protein lev-els.CVB3 RNA was quantified by semi-quantitative RT -PCR as well .Results Compared with myocarditis group, the histopathological damages in myocardium were significantly alleviated in both Ivabradine group and Carvedilol group on days 7 and 14.The expressions of MCP-1,IL-6 and TNF -αat mRNA level were up-regulated in mice treated with Ivabradine and Carvedilol as compared with those in control group .Compared with myocarditis group , the expressions of TNF-αon day4 and IL-6 on day 7 at mRNA level were reduced in Ivabradine and Carvedilol treatment groups .MCP-1 expression at mRNA level was only down-regulated in Iv-abradine group on day 7.Concluison Ivabradine treatment could alleviate histopathological damages in my -ocardium of mice with CVB3-induced viral myocarditis , which was similar to the effects of carvedilol treat-ment.The treatment effects might be associated with the down-regulation of expressions of IL-6, TNF-αand MCP-1 at mRNA and protein levels .

关 键 词：伊伐布雷定 卡维地洛 炎症因子 病毒性心肌炎 

分 类 号：R542.21[医药卫生—心血管疾病]