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

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.

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

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 vivo.