脱氧核酶抗呼吸道合胞病毒感染不同免疫功能小鼠的研究  

Effects of deoxyribozyme against respiratory syncytial virus infection in mice with different immune functions

作　　者：周娟[1] 赵晓东[1] 蒋利萍[1] 杨锡强[1] 

机构地区：[1]重庆医科大学附属儿童医院肾脏免疫科儿童发育疾病研究省部共建教育部重点实验室,400014

出　　处：《中华微生物学和免疫学杂志》2010年第10期902-908,共7页Chinese Journal of Microbiology and Immunology

基　　金：基金项目：国家自然科学基金资助项目（30340045）

摘　　要：目的 研究脱氧核酶（DZ）抗不同免疫功能小鼠呼吸道合胞病毒（RSV）感染的作用.方法 RSV感染BALB/c鼠和裸鼠滴鼻给予DZ,空斑形成试验检测肺组织病毒滴度,RT-PCR检测病毒mRNA表达、支气管肺泡灌洗液白细胞计数,ELISA检测TNF-o、IL-12、IFN-γ和IL-10水平,肺组织病理学分析炎症情况.结果 DZ治疗组BALB/c鼠和裸鼠肺组织病毒滴度比感染对照组下降（P＜0.05）,裸鼠下降更明显（P＜0.01）.0.2 mg、0.4 mg和0.8 mg DZ分别降低感染BALB/c鼠30.51%、47.38%（P＜0.05）、53.97%（P＜0.01）和感染裸鼠36.59%（P＜0.05）、48.72%、59.78%（P＜0.01）病毒mRNA表达.0.4 mg DZ治疗降低感染BALB/c鼠和裸鼠支气管肺泡灌洗液中白细胞总数,改善肺组织病理学损伤（P＜0.05）,降低感染裸鼠气道局部TNF-α、IL-12和IFN-γ分泌（P＜0.05）.结论 DZ在不同免疫功能小鼠体内有效抑制RSV复制,减轻气道炎症,对裸鼠的保护作用更突出,是有效的抗RSV制剂.Objective To investigate the effects of deoxyribozyme（DZ） against respiratory syncytial virus（RSV） infection in BALB/c mice and nude mice. Methods RSV infected BALB/c mice and nude mice were nasally dripped with DZ. Pulmonary viral titers were detected by plaque forming experiment,and viral mRNA expression was assayed by RT-PCR. Leukocytes and the subgroup cells in bronchoalveolar lavage fluid （BALF） were counted, cytokines of TNF-α, IL-12, IFN-γand IL-10 in BALF were assayed by ELISA. Pulmonary histopathology was examined to realize the inflammation of airway. Results Pulmonary titers of 0.2 mg, 0.4 mg and 0.8 mg DZ treated BALB/c mice were lg（3.65 ±0.12） PFU/g lung,lg（ 3.25 ± 0.10） PFU/g lung and lg（ 3.03 ±0.08 ） PFU/g lung, decreased as compared with that of infected control BALB/c mice lg（4.35 ± 0.11 ） PFU/g lung （ P〈0.05 ）. Meanwhile viral titers of 0.2 mg,0.4 mg and 0.8 mg DZ treated nude mice were lg（4.82 ±0.15） PFU/g lung, lg（4.47 ±0.12） PFU/g lung and lg（4.21 ±0.11 ） PFU/g lung, declined dramatically as compared with that of infected control nude mice lg（6.23 ± 0.15） PFU/g lung（ P〈0.01 ）. 0.2 mg, 0.4 mg and 0.8 mg DZ reduced BALB/c mice pulmonary viral mRNA expression by 30.51% ,47.38% （ P〈0.05 ） and 53.97% （ P〈0.01 ） and nude mice by 36.59% （P 〈0.05 ）, 48.72%, 59.78% （ P〈0.01 ） respectively as compared with their infected control groups. In 0.4 mg DZ treated BALB/c mice and nude mice, total numbers of leukocytes in BALF were decreased dramatically and pulmonary histology was significantly improved compared with their infected controls（ P〈0.05 ）. And the treatment of 0.4 mg DZ reduced productions of TNF-α, IL-12 and IFN-γin BALF of RSV infected nude mice （ P〈0.05 ）. Conclusion DZ effectively inhibits viral replication and reduces airway inflammation in RSV infected BALB/c mice and nude mice, and the effects in nude mice are more significant. DZ is a potential therapeutic agent against RSV infection in

关 键 词：呼吸道合胞病毒 脱氧核酶 免疫 基因治疗 

分 类 号：R[医药卫生]