期刊：
Journal of Ethnopharmacology,2024年328:118010 ISSN：0378-8741
通讯作者：
Tan, Nianhua;Tian, Xuefei;Chen, Bin
作者机构：
[Tian, Xuefei; Tan, Nianhua; Jian, Gonghui] College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, China;[Tan, Nianhua] Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan Province, China. Electronic address: l00342@hnucm.edu.cn;[Peng, Jie] Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan Province, China;[Tian, Xuefei] Hunan Province University Key Laboratory of Oncology of Traditional Chinese Medicine Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China;[Tian, Xuefei] Key Laboratory of Traditional Chinese Medicine for Mechanism of Tumor Prevention &Treatment, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. Electronic address: 003640@hnucm.edu.cn
通讯机构：
[Tan, Nianhua; Chen, Bin] D;[Tian, Xuefei] K;Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan Province, China. Electronic address:;Key Laboratory of Traditional Chinese Medicine for Mechanism of Tumor Prevention &Treatment, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. Electronic address:;Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan Province, China. Electronic address:
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal pair Paeoniae Radix Rubra (roots of Paeonia lactiflora Pall., Chishao in Chinese) and Aconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi in Chinese) are widely used for the treatment of liver diseases, demonstrating clinical efficacy against acute-on-chronic liver failure (ACLF). As the core drug pair representing the "clearing method" and "warming method" in traditional Chinese medicine (TCM), they align with the TCM syndromic characteristics of ACLF, characterized by a mixture of deficiencies and realities. However, the molecular mechanisms underlying the anti-ACLF effects of Chishao - Fuzi herbal pair remain unclear. AIM OF THE STUDY: To reveal the immunoinflammatory status of patients with hepatitis B virus-related ACLF (HBV-ACLF) based on macrophage polarization and to explore the mechanism of action of Chishao - Fuzi herbal pair in regulating macrophage polarization against ACLF. MATERIALS AND METHODS: Peripheral blood samples were prospectively obtained from patients with HBV-ACLF, patients with chronic hepatitis B (CHB) in the immunoactive phase and healthy individuals. Flow cytometry, qRT-qPCR, and ELISA were used to reveal the activation status of monocyte-macrophages and the expression differences in related cytokines in the peripheral blood of patients with HBV-ACLF. Then, an ACLF rat model and a macrophage inflammation model in vitro were established. Hematoxylin-eosin staining, immunohistochemical staining, transmission electron microscopy, flow cytometry, western blotting, RT-qPCR, and ELISA were used to observe changes in the expression of M1/M2 macrophage markers and related inflammatory factors after Chishao - Fuzi herbal pair intervention, both in vivo and in vitro. RESULTS: Patients with HBV-ACLF exhibited an imbalance in M1/M2 macrophage polarization, showing a tendency to activate M1 macrophages with high expression of CD86 and iNOS. This imbalance led to an increase in relevant pro-inflammatory factors (IL-1β, IL-6, TNF-α) and a decrease in anti-inflammatory factors (IL-10, TGF-β, VEGF), exacerbating the uncontrolled immune-inflammatory response. Chishao - Fuzi herbal pair intervention improved liver function, coagulation function, and histopathological injury in ACLF rats. It also partially ameliorated endotoxemia and inflammatory injury in ACLF. The mechanism was to restore the immune-inflammatory imbalance and prevent the exacerbation of inflammatory response to liver failure by promoting macrophage polarization toward M2 anti-inflammatory direction, inhibiting M1 macrophage activation, and increasing the levels of anti-inflammatory factors and decreasing pro-inflammatory factors. CONCLUSION: Chishao - Fuzi herbal pair can reduce the systemic inflammatory burden of liver failure by modulating macrophage polarization and restoring ACLF immune-inflammatory imbalance. This study provides new perspectives and strategies for studying HBV-ACLF immune reconstitution and inflammatory response control.
摘要：
Acute-on-chronic liver failure (ACLF) is a progressive disease that is associated with rapid worsening of clinical symptoms and high mortality. A multicentre prospective study from China demonstrated that patients with hepatitis B virus-related ACLF (HBV-ACLF) exhibited worse clinical characteristics and higher mortality rates compared to non-HBV-ACLF patients. Immune dysregulation is closely linked to the potential mechanisms of initiation and progression of ACLF. Innate immune response, which is represented by monocytes/macrophages, is up-regulated across ACLF development. This suggests that monocytes/macrophages play an essential role in maintaining the immune homeostasis of ACLF. Information that has been published in recent years shows that the immune status and function of monocytes/macrophages vary in ACLF precipitated by different chronic liver diseases. Monocytes/macrophages have an immune activation effect in hepatitis B-precipitated-ACLF, but they exhibit an immune suppression in cirrhosis-precipitated-ACLF. Therefore, this review aims to explain whether this difference affects the clinical outcome in HBV-ACLF patients as well as the mechanisms involved. We summarize the novel findings that highlight the dynamic polarization phenotype and functional status of hepatic macrophages from the stage of HBV infection to ACLF development. Moreover, we discuss how different HBV-related liver disease tissue microenvironments affect the phenotype and function of hepatic macrophages. In summary, increasing developments in understanding the differences in immune phenotype and functional status of hepatic macrophages in ACLF patients will provide new perspectives towards the effective restoration of ACLF immune homeostasis.
作者机构：
[曹钰楠; 唐陈琴; 谭年花] Hunan University of Chinese Medicine, Changsha, 410208, China;[彭杰; 陈斌] The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China
通讯机构：
[Chen, B.] T;The First Affiliated Hospital of Hunan University of Chinese MedicineChina
