基于GC-MS的吉德生蛇丸治疗蝮蛇毒中毒小鼠代谢组学分析
Metabolomic analysis of Agkistrodon haly venom poisoning mouse treatment by Jidesheng snake pill based on GC-MS.
发表日期:2024
作者:
Jie Luo, Minkang Guo, Ke Xie, Ting-Li Han, Shanmu Ai
来源:
Frontiers in Pharmacology
摘要:
蛇咬伤是蛇毒经伤口进入体内引起的急性全身中毒性疾病。未能立即使用抗蛇毒血清和难以获得抗蛇毒血清通常是导致疾病恶化的原因。治疗蛇咬伤时,常用中药补充或替代抗蛇毒血清。济德生蛇丸(JDS)是一种广泛使用的中药,在临床上取得了良好的治疗效果;然而,其机制仍不清楚。因此,采用代谢组学技术探讨JDS治疗Agkistrodon halys(Ah)蛇毒中毒小鼠的病理生理机制。通过小鼠后腿肌肉注射Ah毒液建立Ah组小鼠模型。采用阿毒治疗患部后,采用JDS建立阿毒JDS组模型。苏木精和伊红(HE)染色用于评估腓肠肌损伤的严重程度。采用定量聚合酶链反应(qPCR)检测血管细胞粘附分子-1(VCAM-1)、肌肉特异性肌酸激酶(CKM)、凝血酶抗凝血酶复合物(TAT)和肿瘤坏死因子-α的mRNA表达。肿瘤坏死因子-α)。气相色谱-质谱 (GC-MS) 进行多变量统计分析,为阿毒中毒小鼠的整体代谢概况提供新的见解。HE 染色显示阿毒中红细胞坏死、局部出血和中性粒细胞浸润增加组高于对照组。鉴定出多种化合物,包括脂质、氨基酸、肽和有机氧。在对照组和Ah毒液组之间筛选出80种差异代谢物,在Ah毒液组和JDS组之间筛选出24种差异代谢物。小鼠Ah毒中毒的机制可能涉及氨酰-tRNA生物合成、各种氨基酸代谢障碍、三羧酸循环障碍、脂肪酸代谢异常等。 JDS可能通过影响长链脂肪酸和氨基酸代谢,促进烟酰胺-烟酰胺代谢来减轻症状。我们的研究结果表明,代谢组学对于阐明蝮蛇毒液中毒的病理生理学和JDS的治疗机制具有巨大的前景。Copyright © 2024 Luo,郭、谢、韩、艾。
Snakebites are acute systemic toxic diseases caused by snake venom entering the body through wounds. Failure to use antivenom immediately and difficulty in obtaining antivenoms are frequently responsible for worsening disease. Traditional Chinese medicine is commonly used to supplement and replace antivenom in treating snakebites. The Jidesheng snake pill (JDS) is a widely used traditional Chinese medicine that has achieved good clinical therapeutic effects; however, its mechanism remains unclear. Therefore, metabolomics techniques were employed to explore the pathophysiological mechanisms of JDS treatment of Agkistrodon halys (Ah) snake venom-poisoned mice.The Ah group mouse model was established by intramuscular injection of Ah venom into the hind legs of the mice. The Ah venom + JDS group model was established using JDS after the affected area was treated with Ah venom. Hematoxylin and eosin (HE) staining was used to evaluate the severity of gastrocnemius injury. Quantitative polymerase chain reaction (qPCR) was utilized to detect the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), muscle-specific creatine kinase (CKM), thrombin antithrombin complex (TAT), and tumor necrosis factor-alpha (TNF-α). Gas chromatography-mass spectrometry (GC-MS) was performed with multivariate statistical analysis to provide new insights into the global metabolic profile of Ah venom-poisoned mice.HE staining revealed increased red cell necrosis, local hemorrhage, and neutrophil infiltration in the Ah venom group than in the control group. Several compounds were identified, including lipids, amino acids, peptides, and organooxygen. Eighty differential metabolites were screened between the control group and the Ah venom group, and 24 were screened between the Ah venom and JDS groups. The mechanism of Ah venom poisoning in mice may involve aminoacyl-tRNA biosynthesis, various amino acid metabolism disorders, tricarboxylic acid circulation disorders, and abnormal fatty acid metabolism. JDS may reduce symptoms by affecting long-chain fatty acid and amino acid metabolism and promoting nicotinamide-nicotinamide metabolism.Our results suggest that metabolomics has huge prospects for elucidating the pathophysiology of Agkistrodon haly venom poisoning and therapeutic mechanisms of JDS.Copyright © 2024 Luo, Guo, Xie, Han and Ai.