古方麻黄连翘赤小豆汤通过抑制血管性血友病因子信号通路保护急性和慢性肝衰竭。
Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling.
机构信息
Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Department of Emergency Internal Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
出版信息
Cells. 2022 Oct 25;11(21):3368. doi: 10.3390/cells11213368.
BACKGROUND
Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases.
METHODS
The LPS/D-GalN-induced ALF mice model and the CCl+LPS/D-GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses.
RESULTS
MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment.
CONCLUSIONS
Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.
背景
急性肝衰竭（ALF）和慢加急性肝衰竭（ACLF）的特征是全身炎症和高死亡率，但目前尚无有效的临床治疗方法。麻黄连翘赤小豆汤（MHLQD）作为一种经典的传统中药（TCM）配方，已在临床上用于治疗肝脏疾病数百年。
方法
使用 LPS/D-GalN 诱导的 ALF 小鼠模型和 CCl+LPS/D-GalN 诱导的 ACLF 小鼠模型，观察 MHLQD 对小鼠死亡率、肝细胞死亡、肝损伤和免疫反应的治疗作用。
结果
MHLQD 治疗可显著提高小鼠的存活率。MHLQD 治疗后肝损伤和全身及肝脏免疫反应也得到改善。机制上，分析了 MHLQD 处理的肝组织中的蛋白质组变化，结果表明 MHLQD 处理的 ALF 和 ACLF 模型中血栓形成的血管性血友病因子（VWF）显著受到抑制。组织学染色和 Western blot 证实，MHLQD 处理的 ALF 和 ACLF 模型中 VWF/RAP1B/ITGB3 信号受到抑制。此外，用 VWF 抑制剂 ADAMTS13 处理的小鼠显示出对 MHLQD 治疗的疗效降低。
结论
我们的研究表明，MHLQD 是治疗 ALF 和 ACLF 的有效中药方剂，其可能归因于通过 VWF/RAP1B/ITGB3 信号保护肝细胞免于死亡。
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