基于miRNA介导的ERAD-ERSIA稳态失衡探讨肺癌恶病质正虚伏毒病机

Pathogenesis of healthy qi deficiency with latent toxins in lung cancer cachexia based on miRNA-mediated ERAD-ERSIA homeostatic imbalance

肺癌恶病质(lung cancer cachexia,LCC)是肺癌中晚期的常见并发症。现代医学营养支持仅在一定程度上缓解LCC,总体疗效欠佳。恶病质属于中医学“虚劳”范畴,继发于肺癌的LCC又有其特有的病机特点。正虚伏毒是LCC的重要病机,探索并丰富该病机的科学内涵有重要意义。骨骼肌萎缩是LCC的重要特征之一,与内质网应激(endoplasmic reticulum stress,ERS)息息相关。适度的ERS时,内质网应激相关性降解(ER-associated degradation,ERAD)被激活,能有效恢复肌细胞内环境稳态,维持其存活;持续或高强度ERS时,内质网应激性凋亡(endoplasmic reticulum stress induced apoptosis,ERSIA)被激活,引起肌细胞凋亡,导致骨骼肌萎缩。miRNA是调控ERAD-ERSIA稳态的上游潜在靶点,从miRNA介导的ERAD-ERSIA稳态失衡探讨LCC正虚伏毒的病机,可为中医药改善LCC临床疗效提供思路。

Lung cancer cachexia(LCC)is a common complication of advanced lung cancer.It can only be alleviated to a certain extent by nutritional support of modern medicine with unsatisfied effects.Cachexia belongs to the category of"deficiency consumption"in Chinese medicine,and the one secondary to lung cancer has its unique pathogenetic characteristics.It is important to explore and enrich the scientific connotation of healthy qi deficiency with latent toxins,which is the important pathogenesis of LCC.As one of the important features of LCC,skeletal muscle atrophy is closely related to endoplasmic reticulum stress(ERS).ER-associated degradation(ERAD)is activated under moderate endoplasmic reticulum stress,so as to effectively restore the internal environment homeostasis of myocyte and maintain its survival;while endoplasmic reticulum stress induced apoptosis(ERSIA)is activated under sustained or high-intensity endoplasmic reticulum stress,causing myocyte apoptosis and resulting in skeletal muscle atrophy.Since miRNA is a potential target upstream for regulating ERAD-ERSIA homeostasis,the pathogenesis of healthy qi deficiency with latent toxins in LCC based on miRNA-mediated ERAD-ERSIA homeostatic imbalance should be explored,which can provide reference to improve the clinical effects of TCM for LCC.