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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。
OBJECTIVE: To establish an animal model of viral myocarditis in BALB / c mice infected with enterovirus 71 (EV71) and use 3-ribavirin for interventional therapy to observe the curative effect of the drug and provide a basis for its clinical application . Methods One-day-old BALB / c mice were randomly divided into 6 groups: normal control group, model group, low dosage of 3-ribavirin, middle dosage of 3-ribavirin, Nucleoside high-dose group and 3-ribavirin positive drug control group. The EV71 laboratory strain was used to infect mice by intraperitoneal (IP) and heart samples were collected for virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) identification of myocardial tissue. Meanwhile, myocardial tissue The pathological changes were observed and the levels of serum creatine kinase isoenzymes (CK-MB) were measured. Results After intraperitoneal inoculation of EV71, the infected mice showed varying degrees of clinical manifestations or even death. Myocardial tissue virus isolation, RT-PCR identification, histopathological changes, myocardial enzymes CK-MB abnormal increase were proven successful modeling; compared with the model group, 3-ribavirin dose of each group of mice clinical symptoms (P <0.05). The levels of CK-MB in myocardium decreased and the mortality rate decreased in the mice (all P <0.05). Conclusion EV71 infection can cause myocarditis in mice. 3-ribavirin can significantly improve the clinical symptoms of viral myocarditis caused by EV71, reduce the mortality of mice, reduce serum levels of myocardial enzymes, have a certain therapeutic effect.