National Center for Protein Science (Shanghai), Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 201210, China.
Tianjin Institute of Pharmaceutical Research , Tianjin 300193, China.
J Proteome Res. 2017 Nov 3;16(11):4009-4019. doi: 10.1021/acs.jproteome.7b00409. Epub 2017 Oct 2.
ShuFengJieDu capsule (SFJDC), a traditional Chinese medicine (TCM) that contains eight medicinal herbs, has been extensively utilized for the treatment of acute lung injury (ALI) and respiratory infections for more than 30 years in China. SFJDC has also been listed in the official guidelines of the China Food and Drug Administration (CFDA) due to its stable clinical manifestations. However, the underlying mechanism of SFJDC during ALI repair remains unclear. In the present study, we explored the protective and therapeutic mechanisms of SFJDC in a rat model by performing qualitative and label-free quantitative proteomics studies. After establishing lipopolysaccharide (LPS)-induced ALI rat models, we profiled macrophage cells isolated from freshly resected rat lung tissues derived from ALI models and ALI rat lung tissue sections using a high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) shotgun proteomics approach to identify changes in the expression levels of proteins of interest. On the basis of our proteomics results and the results of a protein dysregulation analysis of ALI rat lung tissues and rat lung macrophages, AKT1 was selected as a putative key factor that may play an important role in mediating the effects of SFJDC treatment during ALI progression. Follow-up validation studies demonstrated that AKT1 expression effectively regulates various ALI-related molecules, and Gene Ontology analysis indicated that SFJDC-treated ALI rat macrophages were influenced by AKT1-based networks. Gain- and loss-of-function analyses following lentivirus-AKT1 or lentivirus-si-AKT1 infection in macrophages also indicated that AKT1 was essential for the development of ALI due to its ability to regulate oxidative stress, apoptosis, or inflammatory responses. In summary, SFJDC effectively modulated anti-inflammatory and immunomodulation activity during ALI, potentially due to AKT1 regulation during ALI progression. New insights into SFJDC mechanisms may facilitate the development of novel pharmaceutical strategies to control the expression of inflammatory factors.
疏风解毒胶囊（SFJDC）是一种中药，含有八种草药，在中国已广泛用于治疗急性肺损伤（ALI）和呼吸道感染超过 30 年。SFJDC 也因其稳定的临床疗效而被列入中国食品药品监督管理局（CFDA）的官方指南。然而，SFJDC 在 ALI 修复中的潜在机制尚不清楚。在本研究中，我们通过定性和无标记定量蛋白质组学研究探索了 SFJDC 在大鼠模型中的保护和治疗机制。在建立脂多糖（LPS）诱导的 ALI 大鼠模型后，我们使用高效液相色谱-质谱（HPLC-MS/MS）shotgun 蛋白质组学方法对从 ALI 模型和 ALI 大鼠肺组织切片中分离的巨噬细胞进行了蛋白质组学分析，以鉴定感兴趣的蛋白质表达水平的变化。基于我们的蛋白质组学结果以及 ALI 大鼠肺组织和大鼠肺巨噬细胞中蛋白质失调分析的结果，AKT1 被选为一个可能的关键因素，可能在介导 SFJDC 在 ALI 进展过程中的治疗作用中发挥重要作用。后续验证研究表明，AKT1 表达有效地调节各种 ALI 相关分子，GO 分析表明，SFJDC 处理的 ALI 大鼠巨噬细胞受到 AKT1 网络的影响。在巨噬细胞中进行慢病毒-AKT1 或慢病毒-si-AKT1 感染的增益和失能分析也表明，由于 AKT1 能够调节氧化应激、细胞凋亡或炎症反应，因此 AKT1 对 ALI 的发生是必不可少的。总之，SFJDC 在 ALI 期间有效地调节抗炎和免疫调节活性，这可能是由于 AKT1 在 ALI 进展过程中的调节作用。对 SFJDC 机制的新认识可能有助于开发控制炎症因子表达的新型药物策略。
