Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
Department of Food Technology, Faculty of Agro-Industry, Prince of Songkhla University, 90112 Hat Yai, Songkhla, Thailand.
Int Immunopharmacol. 2023 Aug;121:110493. doi: 10.1016/j.intimp.2023.110493. Epub 2023 Jun 16.
Acute lung injury leads to the development of chronic conditions such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma as well as alveolar sarcoma. Various investigations are being performed worldwide to understand the pathophysiology of these diseases, develop novel bioactive compounds and inhibitors to target the ailment. Generally, in vivo models are used to understand the disease outcome and therapeutic suppressing effects for which the animals are chemically or physically induced to mimic the onset of definite disease conditions. Amongst the chemical inducing agents, Bleomycin (BLM) is the most successful inducer. It is reported to target various receptors and activate inflammatory pathways, cellular apoptosis, epithelial mesenchymal transition leading to the release of inflammatory cytokines, and proteases. Mice is one of the most widely used animal model for BLM induced pulmonary associated studies apart from rat, rabbit, sheep, pig, and monkey. Although, there is considerable variation amongst in vivo studies for BLM induction which suggests a detailed study on the same to understand the mechanism of action of BLM at molecular level. Hence, herein we have reviewed various chemical inducers, mechanism of action of BLM in inducing lung injury in vivo, its advantages and disadvantages. Further, we have also discussed the rationale behind various in vivo models and recent development in BLM induction for various animals.
急性肺损伤会导致特发性肺纤维化 (IPF)、慢性阻塞性肺疾病 (COPD)、哮喘以及肺泡肉瘤等慢性疾病的发生。目前,世界各地都在进行各种研究,以了解这些疾病的病理生理学机制,开发针对这些疾病的新型生物活性化合物和抑制剂。通常,体内模型用于了解疾病的结果和治疗抑制作用,为此,动物会受到化学或物理刺激,以模拟特定疾病的发作。在化学诱导剂中,博来霉素 (BLM) 是最成功的诱导剂。据报道,它可以靶向多种受体并激活炎症途径、细胞凋亡、上皮间质转化,导致炎症细胞因子和蛋白酶的释放。除了大鼠、兔子、绵羊、猪和猴子之外,小鼠也是 BLM 诱导肺部相关研究中最广泛使用的动物模型之一。尽管 BLM 诱导的体内研究存在相当大的差异,但需要对其进行详细研究,以了解 BLM 在分子水平上的作用机制。因此,本文综述了各种化学诱导剂、BLM 在体内诱导肺损伤的作用机制、其优缺点。此外,我们还讨论了各种体内模型背后的原理以及 BLM 在各种动物中的诱导的最新进展。