Department of Public Health, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Emergency Department, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, China.
J Tradit Chin Med. 2022 Aug;42(4):622-632. doi: 10.19852/j.cnki.jtcm.20220617.002.
To explore the novel biomarkers and therapeutic target candidates related to the stasis-heat syndrome of acute intracerebral hemorrhage (AICH).
Applying an isobaric tagging for relative and absolute quantitation-(iTRAQ-) based quantitative proteomic approach, plasma samples from AICH patients with stasis-heat, and AICH patients with non-stasis-heat and healthy control subjects were collected and analyzed to distinguish differentially expressed proteins (DEPs) correlated to AICH with stasis-heat in this block design. The standard Western blot was applied to verify DEPs. Additionally, DEPs were analyzed via bioinformatic platforms and further approved via Ingenuity Pathway Analysis (IPA).
A total of 26 DEPs were found among AICH with the stasis-heat, AICH with non-stasis-heat, and healthy control group. The seven DEPs compared with the non-stasis-heat group are closely related to the pathogenesis of stasis heat. These proteins showed three different protein expression patterns. The alpha-1-b glycoprotein (A1BG) and copper-protein (CP) were up-regulated in the stasis-heat group, but down-regulated in the non-stasis-heat group. Compared with the non-stasis-heat group, the expression abundance of actinin, alpha 1 (ACTN1), carbonic anhydrase I (CA1), peroxiredoxin 2 (PRDX2), and vinculin (VCL) is higher in the stasis-heat group, while the CD44 is the opposite. These differences reflect that stasis-heat syndrome has more severe inflammatory immune response, coagulation disorders and damage. Bioinformatics analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of AICH with stasis-heat. AICH with stasis-heat syndrome showed more severe inflammatory reactions, tissue damage, and coagulation disorders than non-stasis heat syndrome.
There are differences in the protein expression patterns between the stasis-heat syndrome and non-stasis-heat syndrome. These differences reflect that stasis-heat syndrome has more severe damage. CD44, CP, ACTN1, CA1, VCL, PRDX2, and A1BG could be the potential biomarkers and therapeutic target candidates of the stasis-heat subtype. This study provides a reasonable explaination for Liangxue Tongyu decoction through anti-inflammatory and brain protection treatment.
探索与急性脑出血（AICH）热瘀证相关的新型生物标志物和治疗靶点候选物。
采用等重同位素标记相对和绝对定量（iTRAQ）定量蛋白质组学方法，采集 AICH 热瘀证患者、AICH 非热瘀证患者和健康对照者的血浆样本，采用块设计对其进行分析，以区分与 AICH 热瘀证相关的差异表达蛋白（DEPs）。采用标准 Western blot 验证 DEPs。此外，通过生物信息学平台对 DEPs 进行分析，并进一步通过 IPA 进行验证。
在 AICH 热瘀证、AICH 非热瘀证和健康对照组中，共发现 26 个 DEPs。与非热瘀证组相比，与热瘀证发病机制密切相关的 7 个 DEP 具有三种不同的蛋白表达模式。α-1-b 糖蛋白（A1BG）和铜蛋白（CP）在热瘀证组中上调，但在非热瘀证组中下调。与非热瘀证组相比，热瘀证组肌动蛋白α 1（ACTN1）、碳酸酐酶 I（CA1）、过氧化物酶 2（PRDX2）和纽蛋白（VCL）的表达丰度较高，而 CD44 则相反。这些差异反映了热瘀证综合征具有更严重的炎症免疫反应、凝血紊乱和损伤。生物信息学分析表明，广泛的细胞和代谢过程以及一些信号通路参与了 AICH 热瘀证的病理生理学过程。与非热瘀证相比，热瘀证 AICH 患者表现出更严重的炎症反应、组织损伤和凝血紊乱。
热瘀证和非热瘀证之间的蛋白表达模式存在差异。这些差异反映了热瘀证具有更严重的损伤。CD44、CP、ACTN1、CA1、VCL、PRDX2 和 A1BG 可能是热瘀证亚型的潜在生物标志物和治疗靶点候选物。本研究通过抗炎和脑保护治疗为凉血通瘀汤提供了合理的解释。
