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左金方通过下调 JAK1/STAT3 信号通路对脓毒症肺损伤的保护作用。

Protective Effect of Zuojin Fang on Lung Injury Induced by Sepsis through Downregulating the JAK1/STAT3 Signaling Pathway.

机构信息

Emergency Department, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, China.

School of Pharmacy, Jiangsu University, Xuefu Road, Zhenjiang, Jiangsu 212013, China.

出版信息

Biomed Res Int. 2021 Jan 6;2021:1419631. doi: 10.1155/2021/1419631. eCollection 2021.

Abstract

Lung injury was the common and serious complication of sepsis, a systemic inflammatory response syndrome caused by severe infections. Chinese medicine had unique advantages in attenuating inflammatory response, such as Zuojinfang (ZJF). ZJF was a classical compound herb formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6 : 1. In this paper, 15 ingredients in ZJF were identified and 8 of them absorbed into rat's serum were quantified by HPLC-MS/MS. Subsequently, sepsis-induced lung injury model was replicated in rats by cecal ligation and puncture. 60 SD rats were randomly divided into 6 groups ( = 10): control group (CON), sham group (Sham), model group (MOD), ZJF low-dose group (ZJF-L), ZJF high-dose group (ZJF-H), and prednisolone group (PNSL). Within the next 24 h, the levels of inflammatory factors, correlation between active ingredients and inflammatory cytokines, the pathological changes of lung tissue, and protein expression of the JAK1/STAT3 signaling pathways were analyzed one by one. Finally, the concentration order of components absorbed in rat serum was berberine > palmatine > jatrorrhizine > coptisine > evodin > chlorogenic acid > evodiamine. Compared with the MOD group, the TNF-, IL-6, and IFN- in the ZJF-H group were significantly reduced ( < 0.05). Moreover, the TNF- decreased significantly accompanied by the increase of berberine, chlorogenic acid, jatrorrhizine, palmatine, evodin, and evodiamine in serum (negative correlation, < 0.05). Compared with the MOD, the area of lung injury, the expressions of JAK1, p-JAK1, STAT3, and p-STAT3 were significantly decreased under the treatment of ZJF ( < 0.05). Therefore, downregulating the JAK1/STAT3 signaling pathways was a potential avenue of ZJF in reversing lung injury induced by sepsis.

摘要

肺损伤是脓毒症的常见且严重的并发症,脓毒症是由严重感染引起的全身炎症反应综合征。中药在减轻炎症反应方面具有独特的优势,如左金方(ZJF)。ZJF 是一种由黄连和吴茱萸以 6:1 的比例组成的经典复方草药配方。在本文中,鉴定了 ZJF 中的 15 种成分,并通过 HPLC-MS/MS 定量了其中 8 种进入大鼠血清的成分。随后,通过盲肠结扎和穿刺在大鼠中复制脓毒症诱导的肺损伤模型。将 60 只 SD 大鼠随机分为 6 组(每组 10 只):对照组(CON)、假手术组(Sham)、模型组(MOD)、ZJF 低剂量组(ZJF-L)、ZJF 高剂量组(ZJF-H)和泼尼松龙组(PNSL)。在接下来的 24 小时内,分析了炎症因子水平、活性成分与炎症细胞因子的相关性、肺组织的病理变化以及 JAK1/STAT3 信号通路的蛋白表达。最后,按大鼠血清中吸收成分的浓度顺序依次为小檗碱 > 巴马汀 > 药根碱 > 黄连碱 > 吴茱萸碱 > 绿原酸 > 吴茱萸次碱。与 MOD 组相比,ZJF-H 组的 TNF-α、IL-6 和 IFN-γ水平显著降低( < 0.05)。此外,血清中 TNF-α显著降低,同时伴随小檗碱、绿原酸、药根碱、巴马汀、吴茱萸碱和吴茱萸次碱的增加(负相关, < 0.05)。与 MOD 组相比,ZJF 治疗后肺损伤面积、JAK1、p-JAK1、STAT3 和 p-STAT3 的表达均显著降低( < 0.05)。因此,下调 JAK1/STAT3 信号通路是 ZJF 逆转脓毒症引起的肺损伤的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b23e/7808815/71639a642917/BMRI2021-1419631.001.jpg

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