Yan Shifan, Jiang Yu, Yu Ting, Hou Changmiao, Xiao Wen, Xu Jing, Wen Huili, Wang Jingjing, Li Shutong, Chen Fang, Li Shentang, Liu Xiehong, Tan Hao, Zou Lianhong, Liu Yanjuan, Zhu Yimin
Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), 69 Jiefang Western Road, Changsha, 410000, Hunan, People's Republic of China.
Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Changsha, Hunan, China.
Chin Med. 2023 Apr 17;18(1):39. doi: 10.1186/s13020-023-00744-6.
Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear.
To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF-MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1.
SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase.
SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect.
脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍，目前仍缺乏有效的治疗策略。升降散（SJS）是一种著名的中药方剂，已在临床上广泛应用。然而，其在脓毒症诱导的肺损伤中的作用仍不清楚。
为了探究其具体机制，我们首先采用盲肠结扎和穿刺（CLP）建立脓毒症动物模型，并用脂多糖（LPS）加三磷酸腺苷（ATP）处理小鼠肺泡巨噬细胞（MH-S）。然后，利用超高效液相色谱/四极杆飞行时间串联质谱（UPLC/Q-TOF-MS/MS）鉴定其活性成分。进行网络药理学分析以揭示潜在机制。进行苏木精-伊红（HE）染色和生化分析以验证其治疗效果。采用酶联免疫吸附测定（ELISA）检测促炎和抗炎细胞因子的释放。利用蛋白质免疫印迹法（Western blot）检测Gasdermin D（GSDMD）、NLR家族含pyrin结构域蛋白3（NLRP3）、P65、凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1（caspase-1）的蛋白水平。
升降散可显著提高脓毒症小鼠的存活率。此外，它能够在CLP术后第1天抑制促炎细胞因子的释放，而在第7天促进其产生，表明升降散可在早期减轻失控的炎症反应，并在后期改善免疫抑制。网络药理学分析表明，细胞焦亡是升降散在保护脓毒症诱导的肺损伤中发挥的关键作用。蛋白质免疫印迹数据表明，升降散可在脓毒症早期减轻细胞焦亡，而在后期增强细胞焦亡。
升降散通过其双向调节作用减轻脓毒症诱导的肺损伤。
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