CAJ | 학술논문

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。
목적：대비연구단순강저심솔약물이벌포뢰정화β수체조단제잡유지락대가살기B3（ CVB3）병독성심기염소서적작용，탐토이벌포뢰정화잡유지락대급성병독성심기염소서심기염증인자적영향。방법수궤장150지웅성BALB/c소서분위4조：공백대조조（ n＝30），심기염조（ n＝40），이벌포뢰정조（n＝40），잡유지락조（n＝40）。후3조경복강접충CVB3유발급성병독성심기염，공백조복강주사린산완충액，접충당천기위제0천，24 h후이벌포뢰정조화잡유지락조매일관위분별급여이벌포뢰정10 mg/kg、잡유지락10 mg/kg，공백조급여린산염완충액관위，직지제14천말。우접충제4천、7천、14천수궤종각조추취소서측심솔후처사취심장。소서심기병리절편HE염색관찰염증병리개변，반정량RT-PCR검측심기병독RNA，반정량RT-PCR화ELISA법검측심기조직MCP-1、IL-6급TNF-αmRNA화단백수평。결과여심기염조비교，7 d、14 d이벌포뢰정화잡유지락조심기병리손상명현감경。여공백조비교，심기염조재제4천、7천심기MCP-1、IL-6급TNF-α적전록수평명현상조，여심기염조비교，제4천이벌포뢰정조화잡유지락조심기TNF-α전록균하조，제7천량자IL-6적전록하조，부이벌포뢰정조MCP-1전록하조。단백수평개변화mRNA기본일치。결론이벌포뢰정구유화잡유지락상사지감경심기염소서적심기염증손해적작용，기현저하조TNF-α화IL-6 mRNA급단백수평，효과여잡유지락상사，차외，이벌포뢰정환능현저하조MCP-1적mRNA화단백수평。
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 .