二氢杨梅素在M1/M2型巨噬细胞水平对刀豆蛋白A诱导的小鼠免疫性肝炎的调控作用
Regulation of Concanavalin A-induced Immune Hepatitis in Mice by Dihydromyricetin at the M1/M2 Type Macrophage Level.
作者信息
Zhang Xinpeng, Liu Yan, Yang Kaijin, Tang Jichao, Zhao Kang, Li Yi
机构信息
Department of General Surgery, Section for Day Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, 610031 Chengdu, Sichuan, China.
Department of Pathology, Chengdu Women and Children's Central Hospital, 610031 Chengdu, Sichuan, China.
出版信息
Discov Med. 2025 Jan;37(192):64-72. doi: 10.24976/Discov.Med.202537192.6.
BACKGROUND
Autoimmune hepatitis (AIH) is an autoimmune disease accompanied by an autoimmune inflammatory response that often leads to severe liver damage. In addition, it may further lead to complications such as liver fibrosis, cirrhosis and liver failure. Dihydromyricetin (DHM) possesses various pharmacological properties, such as being anti-inflammatory, antioxidant, and antibacterial. In this experiment, we investigated the effect of DHM on autoimmune hepatitis mice based on the level of M1/M2 type macrophages.
METHODS
An autoimmune hepatitis mouse model was established by the administration of DHM followed by tail vein injection of Concanavalin A (Con A). Liver tissues were examined for pathological and morphological changes. Interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-4 (IL-4) levels in liver tissues were assessed. Serum hepatic function indexes were measured, including alanine aminotransferase (ALT), aspartate transaminase (AST), and lactatedehydrogenase (LDH). Oxidative stress indexes, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Nitric oxide (NO), were quantified. Additionally, tumor necrosis factor-α () and nuclear factor kappa-B () mRNA and protein expression polarization were determined. The presence of M1/M2-type macrophages was also investigated.
RESULTS
Compared to the model group, mice in the DHM group exhibited a significant reduction in serum hepatic function indexes ( < 0.05). Liver tissues from the DHM group showed a noteworthy decrease in MDA and NO levels, along with a significant increase in SOD and GSH-Px levels ( < 0.05). Furthermore, in the liver tissues of mice from the DHM group, there was a notable reduction in the count of M1-type macrophages and a considerable elevation in the M2-type macrophages ( < 0.05). IL-1β and IL-6 expression levels exhibited a significant decrease, whereas IL-10 and IL-4 levels displayed a significant increase ( < 0.05). Additionally, both and mRNA levels and protein expression experienced a noteworthy decrease ( < 0.05).
CONCLUSION
DHM mitigates the inflammatory response in AIH mice by reducing oxidative stress and modulating macrophage polarization and the TNF-α/NF-κB pathway.
背景
自身免疫性肝炎（AIH）是一种伴有自身免疫性炎症反应的自身免疫性疾病，常导致严重肝损伤。此外，它可能进一步导致肝纤维化、肝硬化和肝衰竭等并发症。二氢杨梅素（DHM）具有多种药理特性，如抗炎、抗氧化和抗菌。在本实验中，我们基于M1/M2型巨噬细胞水平研究了DHM对自身免疫性肝炎小鼠的影响。
方法
通过给予DHM后尾静脉注射刀豆蛋白A（Con A）建立自身免疫性肝炎小鼠模型。检查肝组织的病理和形态变化。评估肝组织中白细胞介素-1β（IL-1β）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）和白细胞介素-4（IL-4）水平。检测血清肝功能指标，包括丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH）。定量氧化应激指标丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和一氧化氮（NO）。此外，测定肿瘤坏死因子-α（TNF-α）和核因子κB（NF-κB）的mRNA和蛋白表达极化情况。还研究了M1/M2型巨噬细胞的存在情况。
结果
与模型组相比，DHM组小鼠血清肝功能指标显著降低（P<0.05）。DHM组肝组织中MDA和NO水平显著降低，SOD和GSH-Px水平显著升高（P<0.05）。此外，DHM组小鼠肝组织中M1型巨噬细胞数量显著减少，M2型巨噬细胞数量显著增加（P<0.05）。IL-1β和IL-6表达水平显著降低，而IL-10和IL-4水平显著升高（P<0.05）。此外，TNF-α和NF-κB的mRNA水平和蛋白表达均显著降低（P<0.05）。
结论
DHM通过降低氧化应激、调节巨噬细胞极化和TNF-α/NF-κB途径减轻AIH小鼠的炎症反应。
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