加巴喷丁体内外抗RSV感染的作用

Gabapentin inhibits respiratory syncytial virus infection in vitro and in vivo

目的探讨加巴喷丁对呼吸道合胞病毒(respiratory syncytial virus,RSV)的抗病毒作用。方法体外实验通过MTS、TCID50、q RT-PCR方法检测不同浓度加巴喷丁对RSV感染的抑制作用,包括细胞活力、病毒复制及细胞因子的变化。体内实验选取4~6周龄C57BL/6小鼠,随机分为空白对照组、RSV感染组、低剂量及高剂量加巴喷丁处理组,连续腹腔注射给药,每日观察体质量变化,HE染色观察小鼠肺部的病理变化,q RT-PCR方法检测肺部病毒载量。结果 1、2、5、10 mmol/L不同浓度加巴喷丁显著增加RSV感染A549细胞的活力;5、10 mmol/L浓度的加巴喷丁可显著降低RSV感染A549细胞的病毒载量,10 mmol/L的加巴喷丁可显著抑制病毒的复制,减少CCL3、CCL5、CXCL2及TNF-α、IL-6、IL-8等趋化因子和炎性因子表达,促进干扰素IFN-α、IFN-β表达;动物实验表明90μg、180μg的加巴喷丁处理组可减轻RSV感染小鼠的体质量变化、改善肺部病理损伤和降低病毒载量。结论加巴喷丁可通过抑制病毒复制,调节趋化因子及炎性因子释放,促进干扰素分泌的方式发挥体内抗病毒作用,对RSV感染的C57BL/6小鼠有一定的治疗作用,可改善肺部病理,为进一步临床应用提供实验依据。

Respiratory syncytial virus（RSV） is a leading cause of severe lower respiratory tract infection ininfants and children. To date, no specific RSV drugs available. This study was designed to examine the in vitro andin vivo effects of gabapentin on RSV replication and pathogenesis induced by this virus. MTS assay was used todetect the cell viability of A549 cells after treatment with different doses of Gabapentin. RSV replication wasmeasured by TCID50, and the expression of cytokines and chemokines were detected by Quantitative PCR（Q-PCR）.Then, 4-6 weeks aged C57 BL/6 mice were injected intraperitoneally and daily with high or low doses of gabapentin atthe day before infection and since the 5 day post infection. The weight changes of mice were recorded and lung histologywere detected with HE staining. Data showed that gabapentin at dose of 1, 2, 5 and 10 mmol/L could rescue RSV-infected cell viability. Furthermore, 10 mmol/L gabapentin also decreased viral replication and lung inflammation, asevidenced by reduced CCL3, CCL5, CXCL2, TNF-α, IL-6, IL-8 and increased IFN-α, IFN-β m RNA levelsfollowing RSV infection. In addition, gabapentin significantly alleviated the loss of body weight and the lung injury ofRSV-infected mice. In conclusion, in vitro and in vivo data suggests that gabapentin might be a potentialtherapeutic approach for RSV-induced lung diseases.