来源：风湿病与关节炎,2023,12（10）:1-5,34.

松萝酸经HMGB1-RAGE信号通路治疗胶原诱导性关节炎大鼠关节炎机制研究（基础研究）

潘晓艺¹，黄　颖²，张　军²，徐　晖²，陆道敏²，刘　灿²，凌　益²，安　阳²

　　【摘　要】目的：探讨松萝酸经高迁移率族蛋白B1（HMGB1）-晚期糖基化终产物受体（RAGE）信号通路治疗胶原诱导性关节炎（CIA）大鼠关节炎的机制。方法：选取SPF级5周龄Wistar雌鼠54只，随机分为空白对照组，模型对照组，松萝酸低、中、高剂量组和羟氯喹组，每组9只。除空白对照组外，其余各组采用Ⅱ型胶原乳剂建立CIA模型。松萝酸低、中、高剂量组分别给予2 mg·kg^-1·d^-1、6 mg·kg^-1·d^-1、54 mg·kg^-1·d^-1松萝酸灌胃，羟氯喹组给予36 mg·kg^-1·d^-1羟氯喹灌胃，空白对照组及模型对照组则予以等量生理盐水灌胃。连续灌胃4周后，处死大鼠，收集血清，取滑膜组织，分别行HE染色病理检测，ELISA法检测白细胞介素-1β（IL-1β）、基质金属蛋白酶（MMP）、血管内皮生长因子（VEGF）含量，Western blot法检测HMGB1、RAGE mRNA表达水平；PCR法检测HMGB1、RAGE蛋白表达量。结果：与模型对照组比较，松萝酸中、高剂量组滑膜增生程度减低，炎性细胞浸润减少，血清HMGB1、IL-1β、MMP、VEGF表达显著下降（P < 0.05），且HMGB1、RAGE蛋白活性、mRNA含量明显降低（P < 0.05）。结论：松萝酸能减少炎性细胞浸润及滑膜细胞增殖，其机制可能与抑制HMGB-RAGE信号通路有关。

　　【关键词】　类风湿关节炎；胶原诱导性关节炎；松萝酸；HMGB1-RAGE信号通路；大鼠

Study on the Mechanism of Usnic Acid Treating Collagen Induced Arthritis in Rats Through HMGB1-RAGE Signal Pathway

PAN Xiao-yi,HUANG Ying,ZHANG Jun,XU Hui,LU Dao-min,LIU Can,LING Yi,AN Yang

　　【ABSTRACT】Objective:To investigate the mechanism of usnic acid in the treatment of collagen induced arthritis（CIA）in rats through HMGB1-RAGE signaling pathway.Methods:A total of 54 SPF grade five-week-old Wistar female mice were selected and randomly divided into a blank control group,a model control group,low,medium,and high dose groups of usnic acid,and a hydroxychloroquine group,with 9 mice in each group.Except the blank control group,the other groups used type Ⅱ collagen emulsion to establish CIA models.The low,medium,and high dose groups of usnic acid were given 2 mg·kg^-1·d^-1,6 mg·kg^-1·d^-1 and 54 mg·kg^-1·d^-1 usnic acid by gavage,while the hydroxychloroquine group was given 36 mg·kg^-1·d^-1 of hydroxychloroquine by gavage.The blank control group and the model control group were given equal amounts of physiological saline by gavage.After continuous gavage for four weeks,rats were euthanized,serum was collected,synovial tissue was taken,and HE staining and pathological detection were performed.ELISA was used to detect the content of IL-1β,MMP and VEGF,Western blot was used to detect the expression levels of HMGB1 and RAGE mRNA,and PCR method was used to detect the expression levels of HMGB1 and RAGE proteins.Results:Compared with the model control group,the medium and high-dose groups of usnic acid showed a decrease in synovial hyperplasia,inflammatory cell infiltration,and the expression of HMGB1,IL-1β,MMP and VEGF in serum significantly reduced（P < 0.05）,and the protein activity of HMGB1 and RAGE,and the content of mRNA significantly reduced（P < 0.05）.Conclusion:Usnic acid can reduce inflammatory cell infiltration and synovial cell proliferation,and its mechanism may be related to the inhibition of the HMGB-RAGE signaling pathway.

　　【Keywords】 rheumatoid arthritis;collagen induced arthritis;usnic acid;HMGB1-RAGE signaling pathway;rats