青藤碱衍生物4EDB的合成、鉴定以及对实验性自身免疫性心肌炎的治疗作用观察
Synthesis and identification of sinomenine derivate 4EDB and its therapeutic effects on mice with experimental autoimmune myocarditis

目的 ·制备青藤碱衍生物4EDB，研究体内4EDB对实验性自身免疫性心肌炎（EAM）小鼠的治疗作用。方法 ·采用随机分组方法，将BALB/c小鼠分为空白对照组、EAM+4EDB组和EAM组，每组6只。免疫开始的第14日开始灌胃给药，5 mg/（kg·d）。第21日处死小鼠，取出心脏做病理切片，并进行天狼星红染色和苏木精-伊红染色（H-E染色）；real-time PCR检测心肌组织相关炎症因子白介素-1（IL-1）、IL-6、IL-17A、转化生长因子-β(TGF-β)的表达。结果 ·与EAM组相比， EAM+4EDB组心肌炎症病理评分降低（P=0.020），纤维化得到缓解，心肌组织炎症因子IL-1、IL-6、IL-17A、TGF-β水平下降（P<0.05）。结论 ·新合成的青藤碱衍生物4EDB对EAM模型小鼠的心肌炎症有缓解作用，其机制可能与其抑制炎症因子表达有关。
： Objective · To synthesize 4EDB, the derivative of sinomenine, and to observe its therapeutic effects on mice with experimental autoimmune myocarditis (EAM). Methods · The BALB/c mice were randomly divided into three groups control group, EAM group and EAM+4EDB group with 6 mice in each group, and then treated with 4EDB [5 mg/(kg·d)] by intragastric administration from the 14th day of immunization until sacrificed on the 21th day. Hematoxylin-eosin (H-E) staining was used to identify the areas of inflammation, and the hematoxylin-picrosirius red staining was used to detect the degree of myocardial fibrosis. The expression levels of related inflammatory factors including IL-1, IL-6, IL-17A and TGF-β in myocardial tissues were detected by real-time PCR. Results · Compared with EAM group, the pathological score of myocardial inflammation decreased in EAM+4EDB group (P=0.020), with myocardial fibrosis alleviated, and the expression levels of inflammatory cytokines including IL-1, IL-6, IL-17A and TGF-β in myocardium reduced (P<0.05). Conclusion · The new derivative of sinomenine, 4EDB, can alleviate the myocarditis in EAM mice, and the inhibition of inflammatory factors may play an important role