The Matrine Derivate MASM Inhibits Recruitment of Gr1hi Monocyte and Alleviates Liver Injury
The Matrine Derivate MASM Inhibits Recruitment of Gr1hi Monocyte and Alleviates Liver Injury
复制标题
DOI：
10.1159/000501384
复制
发表时间：
2019-07
期刊：
影响因子：
3.1
通讯作者：
Wei-Heng Xu;Jing Xu;Fang Xie;Ying-Hua Li;Zhen-lin Hu;Jin-Jin Zhang-Jin;Bin Lu;Jun-Ping Zhang
中科院分区：
文献类型：
--
作者：
Wei-Heng Xu;Jing Xu;Fang Xie;Ying-Hua Li;Zhen-lin Hu;Jin-Jin Zhang-Jin;Bin Lu;Jun-Ping Zhang
背景资料：（6aS，10 S，11 aR，11bR，11 cS）-10-甲氨基十二氢-3a，7a-二氮杂苯并（de）蒽-8-基（MASM）是一种新型苦参碱衍生物，具有较好的抗炎活性。本研究旨在评价MASM对急性和慢性肝损伤的保护作用，并探讨其可能的机制。研究方法：采用四氯化碳（CCl 4）腹腔注射法建立急性和慢性肝损伤模型，通过生化和组织学检查评价MASM对急性和慢性肝损伤的保护作用。不同单核细胞亚群向肝脏中的浸润通过流式细胞术表征和分析。通过实时荧光定量PCR和transwell趋化实验评价MASM对肝非实质细胞的体外作用。结果：MASM能明显减轻CCl 4诱导的急性肝损伤和肝纤维化。同时，Gr 1hi单核细胞在损伤肝脏的浸润和诱导的单核细胞趋化蛋白-1（MCP-1）的表达受到明显抑制。细胞实验表明，MASM不仅降低MCP-1的表达，而且抑制其趋化活性。结论：本研究表明，MASM对肝损伤的保护作用可能是通过抑制Gr 1hi单核细胞向肝脏的浸润和抑制MCP-1的产生和活性来实现的。这些发现为MASM在肝损伤中的保护作用提供了新的见解。
Backgrounds: (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits better anti-inflammatory activity. This study was designed to evaluate the protective effect of MASM on acute and chronic liver injuries and explore the possible mechanisms. Methods: Acute and chronic liver injury models were established by the CCl4 intraperitoneal injection and the protective effect of MASM was assessed by biochemical and histological examination. The infiltration of different monocyte subsets into the liver was characterized and analyzed by flow cytometry. The in vitro effect of MASM on liver nonparenchymal cells was evaluated by real-time PCR and transwell chemotaxis assays. Results: Administration of MASM markedly attenuated acute liver injury and liver fibrosis induced by CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in injured livers and induced hepatic expression of monocyte chemoattractant protein-1 (MCP-1) were greatly inhibited. Cellular experiments demonstrated that MASM not only decreased the expression of MCP-1 but also inhibited its chemotactic activity. Conclusions: This study demonstrates that the protective effect of MASM on liver injury could be contributed to the suppression of Gr1hi monocyte infiltration to the liver and the inhibition of MCP-1 production and activity. These findings provide new insights into the protective role of MASM in liver injury.