School of Basic Medical Sciences, Hangzhou 310053, P. R. China.
The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, P. R. China.
Am J Chin Med. 2023;51(6):1413-1429. doi: 10.1142/S0192415X23500647. Epub 2023 Jul 10.
Hepatic fibrosis (HF) is a wound healing response featuring excessive deposition of the extracellular matrix (ECM) and activation of hepatic stellate cells (HSCs) that occurs during chronic liver injury. As an initial stage of various liver diseases, HF is a reversible pathological process that, if left unchecked, can escalate into cirrhosis, liver failure, and liver cancer. HF is a life-threatening disease presenting morbidity and mortality challenges to healthcare systems worldwide. There is no specific and effective anti-HF therapy, and the toxic side effects of the available drugs also impose a heavy financial burden on patients. Therefore, it is significant to study the pathogenesis of HF and explore effective prevention and treatment measures. Formerly called adipocytes, or fat storage cells, HSCs regulate liver growth, immunity, and inflammation, as well as energy and nutrient homeostasis. HSCs in a quiescent state do not proliferate and store abundant lipid droplets (LDs). Catabolism of LDs is characteristic of the activation of HSCs and morphological transdifferentiation of cells into contractile and proliferative myofibroblasts, resulting in the deposition of ECM and the development of HF. Recent studies have revealed that various Chinese medicines (e.g., , turmeric, , etc.) are able to effectively reduce the degradation of LDs in HSCs. Therefore, this study takes the modification of LDs in HSCs as an entry point to elaborate on the process of Chinese medicine intervening in the loss of LDs in HSCs and the mechanism of action for the treatment of HF.
肝纤维化(HF)是一种慢性肝损伤时发生的细胞外基质(ECM)过度沉积和肝星状细胞(HSCs)激活的创伤愈合反应。HF 作为各种肝病的初始阶段,是一种可逆转的病理过程,如果不加以控制,可进展为肝硬化、肝衰竭和肝癌。HF 是一种危及生命的疾病,给全球医疗系统带来了发病率和死亡率的挑战。目前尚无特异性和有效的抗 HF 治疗方法,且现有药物的毒副作用也给患者带来了沉重的经济负担。因此,研究 HF 的发病机制并探索有效的防治措施具有重要意义。HSCs 曾被称为脂肪储存细胞,调节肝脏生长、免疫和炎症以及能量和营养稳态。静止状态下的 HSCs 不增殖,且储存大量脂滴(LDs)。LDs 的分解代谢是 HSCs 激活和细胞形态转化为收缩和增殖的肌成纤维细胞的特征,导致 ECM 的沉积和 HF 的发展。最近的研究表明,各种中药(如姜黄、虎杖等)能够有效减少 HSCs 中 LDs 的降解。因此,本研究以 HSCs 中 LDs 的修饰为切入点,阐述了中药干预 HSCs 中 LDs 丢失及治疗 HF 的作用机制。