卡维地洛在柯萨奇病毒 B3 诱导的病毒性心肌炎小鼠模型中比美托洛尔具有更强的抗炎和抗病毒作用。
Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol in murine model with coxsackievirus B3-induced viral myocarditis.
机构信息
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, PR China; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
出版信息
Gene. 2014 Sep 1;547(2):195-201. doi: 10.1016/j.gene.2014.06.003. Epub 2014 Jun 4.
AIMS
This study aims to compare the effects of carvedilol and metoprolol in alleviating viral myocarditis (VMC) induced by coxsackievirus B3 (CVB3) in mice.
METHODS
A total of 116 Balb/c mice were included in this study. Ninety-six mice were inoculated intraperitoneally with CVB3 to induce VMC. The CVB3 inoculated mice were evenly divided into myocarditis group (n=32), carvedilol group (n=32) and metoprolol group (n=32). Twenty mice (control group) were inoculated intraperitoneally with normal saline. Hematoxylin and eosin staining and histopathologic scoring were used to investigate the effects of carvedilol and metoprolol on myocardial histopathologic changes on days 3 and 5. In addition, serum cTn-I levels, cytokine levels and virus titers were determined using chemiluminescence immunoassay, enzyme-linked immunosorbent assay and plaque assay, respectively, on days 3 and 5. Finally, the levels of phosphorylated p38MAPK were studied using immunohistochemical staining and Western blotting on day 5.
RESULTS
Carvedilol had a stronger effect than metoprolol in reducing the pathological scores of VMC induced by CVB3. Both carvedilol and metoprolol reduced the levels of cTn-I, but the effect of carvedilol was stronger. Carvedilol and metoprolol decreased the levels of myocardial pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokine, with the effects of carvedilol being stronger than those of metoprolol. Carvedilol had a stronger effect in reducing myocardial virus concentration compared with metoprolol. Carvedilol was stronger than metoprolol in decreasing the levels of myocardial phosphorylated p38MAPK.
CONCLUSIONS
In conclusion, carvedilol was more potent than metoprolol in ameliorating myocardial lesions in VMC, probably due to its stronger modulation of the balance between pro- and anti-inflammatory cytokines by inhibiting the activation of p38MAPK pathway through β1- and β2-adrenoreceptors.
目的
本研究旨在比较卡维地洛和美托洛尔在缓解柯萨奇病毒 B3（CVB3）诱导的小鼠病毒性心肌炎（VMC）中的作用。
方法
共纳入 116 只 Balb/c 小鼠。96 只小鼠腹腔接种 CVB3 诱导 VMC。CVB3 接种小鼠随机分为心肌炎组（n=32）、卡维地洛组（n=32）和美托洛尔组（n=32）。20 只小鼠（对照组）腹腔接种生理盐水。第 3 天和第 5 天，采用苏木精-伊红染色和组织病理学评分观察卡维地洛和美托洛尔对心肌组织病理学变化的影响。此外，分别采用化学发光免疫分析法、酶联免疫吸附试验和空斑试验检测血清 cTn-I 水平、细胞因子水平和病毒滴度。最后，采用免疫组化染色和 Western blot 法检测第 5 天磷酸化 p38MAPK 水平。
结果
卡维地洛在降低 CVB3 诱导的 VMC 病理评分方面的作用强于美托洛尔。卡维地洛和美托洛尔均降低 cTn-I 水平，但卡维地洛的作用更强。卡维地洛和美托洛尔降低心肌促炎细胞因子水平，增加抗炎细胞因子表达，且卡维地洛的作用强于美托洛尔。卡维地洛降低心肌病毒浓度的作用强于美托洛尔。卡维地洛降低心肌磷酸化 p38MAPK 水平的作用强于美托洛尔。
结论
总之，卡维地洛在改善 VMC 心肌损伤方面比美托洛尔更有效，这可能是由于其通过β1-和β2-肾上腺素受体抑制 p38MAPK 通路的激活，从而更有效地调节促炎和抗炎细胞因子之间的平衡。
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