现代中药研究与实践

目的 阐明射干麻黄汤(SGMHD)对基于ΔS-VRP(G)-Luc病毒模型刺激诱导的小鼠急性肺损伤(Acute lung injury,ALI)的保护作用，并探索其可能的作用机制。方法 在二级生物安全实验室(BSL-2)条件下，通过滴鼻方式给予Balb/c小鼠ΔS-VRP(G)-Luc复制子病毒建立病毒相关ALI模型，评价SGMHD对急性肺损伤的保护作用。转录组学预测作用通路后，通过RT-qPCR检测感染复制子病毒后小鼠肺组织中炎症因子的表达变化，Western Blot分析SGMHD对cGAS-STING通路关键蛋白的调控作用。结果 与Model组相比，SGMHD给药后可减轻复制子病毒诱导的小鼠体质量下降，降低肺组织间质增厚和炎症细胞浸润，改善ALI病理变化。转录组分析表明，复制子病毒感染激活cGAS-STING通路，下游炎症因子富集显著，SGMHD处理可部分逆转该异常激活模式。RT-qPCR 结果显示，Model 组肺组织中 TNF-α、IL-6、IL-1β 及 cGAS、STING、IRF-7、CXCL10 mRNA表达极显著上调(P < 0.01)，而高剂量 SGMHD 可显著下调cGAS、STING(P < 0.05)并极显著下调TNF-α、IL-6、IL-1β 、 IRF-7、CXCL10 的表达(P < 0.01)。Western Blot分析进一步表明，模型组的TBK1和CXCL10蛋白水平明显升高(P < 0.05)，STING与IRF-7的表达水平也有所升高，经SGMHD处理后趋向于对照组水平(P < 0.05，P < 0.01)。结论 SGMHD能够减轻ΔS-VRP(G)-Luc复制子病毒诱导的小鼠ALI，其机制可能与抑制cGAS-STING信号通路过度激活、下调CXCL10等炎症介质及相关炎症因子表达有关，从而改善肺部炎症。

Objective To clarify the protective effects of Shegan Mahuang Decoction (SGMHD) on acute lung injury (ALI) induced by a ΔS-VRP(G)-Luc replicon virus in mice and to explore the underlying mechanisms.Methods Under biosafety level-2 (BSL-2) conditions,a virus-related ALI model was established by intranasal inoculation of BALB/c mice with ΔS-VRP(G)-Luc replicon virus.The protective effect of SGMHD was evaluated by monitoring body-weight changes and examining lung histopathology.Transcriptomic analysis was used to predict the signaling pathways involved.The mRNA expression of inflammatory cytokines and cGAS–STING pathway-related genes in lung tissues was measured by RT-qPCR,and the protein levels of key molecules in this pathway were assessed by Western Blot.Results Compared with the model group,SGMHD treatment attenuated virus-induced body-weight loss,reduced interstitial thickening and inflammatory cell infiltration in the lungs,and improved histopathological features of ALI.Transcriptome analysis indicated that infection with the replicon virus activated the cGAS-STING pathway with significant enrichment of downstream inflammatory mediators,whereas SGMHD partially reversed this abnormal activation pattern.RT-qPCR results showed that the mRNA expression levels of TNF-α,IL-6,IL-1β,as well as cGAS,STING,IRF-7 and CXCL10 in lung tissues were significantly upregulated in the model group (P < 0.01).In contrast,high-dose SGMHD treatment significantly downregulated the expression of cGAS and STING (P < 0.05),and markedly reduced the expression levels of TNF-α,IL-6,IL-1β,IRF-7 and CXCL10 (P < 0.01).Western Blot analysis further indicated that the protein levels of TBK1 and CXCL10 in the model group were significantly elevated (P < 0.05),and the expression levels of STING and IRF-7 were also increased.After treatment with SGMHD,they tended toward the levels of the control group (P < 0.05,P < 0.01).Conclusion SGMHD alleviates ΔS-VRP(G)-Luc replicon virus induced ALI in mice.Its protective effect may be associated with suppression of excessive activation of the cGAS-STING signaling pathway and down-regulation of CXCL10 and other inflammatory mediators,thereby improving pulmonary inflammation.