Establishment of a Viral Myocarditis mouse model with enterovirus 71 infection and identification of the effect of 3-azole nitrogen nucleoside on this model
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摘要: 目的 建立肠道病毒71型(enterovirus 71,EV71)感染BALB/c小鼠的病毒性心肌炎动物模型,并利用3-氮唑核苷进行干预治疗,观察药物疗效,为该药的临床应用提供依据。方法 1日龄BALB/c小鼠60只,随机分为6组,即正常对照组、模型组、3-氮唑核苷低剂量组、3-氮唑核苷中剂量组、3-氮唑核苷高剂量组及3-氮唑核苷阳性药物对照组。EV71实验室株采用腹腔注射 (intraperitoneal,IP) 感染小鼠,采集心脏标本进行心肌组织的病毒分离及逆转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)鉴定,同时观察心肌组织病理改变,检测血清肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)水平。结果 腹腔注射接种EV71后,感染小鼠先后出现程度不等的临床表现甚至死亡。心肌组织的病毒分离、RT-PCR鉴定、组织病理学变化、心肌酶CK-MB异常升高等均证明造模成功;与模型组相比,3-氮唑核苷各剂量组小鼠的临床症状均得到缓解,且小鼠的心肌酶CK-MB水平降低、死亡率下降,差异均有统计学意义(均有P<0.05)。结论 EV71感染可导致小鼠心肌炎。3-氮唑核苷可以明显改善EV71致病毒性心肌炎临床症状,降低小鼠死亡率,降低血清心肌酶水平,有一定的治疗作用。Abstract: Objective To establish a viral myocarditis mouse model of enterovirus 71(EV71) infection, and to estimate the curative effect of 3-azole nitrogen nucleoside on this model, and provide the basis of clinical application of the drug. Methods 60 BALB/c mice were randomly divided into six groups, as the normal control group, model group, 3-azole nitrogen nucleoside low dose group, 3-azole nitrogen nucleoside medium dose group, 3-azole nitrogen nucleoside high dose group to 3-azole nitrogen nucleoside positive control group. The mice were injected with EV71 laboratory strain through intraperitoneal (IP). After sacrifice, the serum and heart tissue of each mouse were collected. The heart tissue were used for virus isolation, reverse transcription-polymerase chain reaction(RT-PCR) and pathologic examination. The changes of creatine kinase isoenzymes (CK-MB) in serum were determined. Results Infected mice successively demonstrated varying clinical symptoms and even death. The models were proved successfully with virus isolation from heart tissue, the results of RT-PCR, the changes of histopathology and the high level of CK-MB. Compared with the model group, the clinical manifestation was alleviated, and the level of CK-MB and mortality were obviously reduced. There were significant differences (all P<0.05), especially the high dose of 3-azole nitrogen nucleoside group. Conclusions The mouse could be infected with EV71 and lead to vital myocarditis. 3-azole nitrogen nucleoside could improve the clinical symptoms; reduce the mortality, and alleviate the damage in the heart tissue, which is benefit to cure vital myocarditis.
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Key words:
- Enterovirus A human /
- Myocarditis /
- Ribavirin
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