来源：风湿病与关节炎,2023,12（9）:1-5,16.

松萝提取物对胶原诱导性关节炎大鼠高迁移率族蛋白B1介导的细胞自噬及炎症因子的影响（基础研究）

文　红¹，安　阳²，张　军¹，徐　晖²，陆道敏²，曹跃朋²，宁乔怡²，王　莹²

　　【摘　要】目的：研究松萝提取物对胶原诱导性关节炎（CIA）大鼠滑膜细胞中凋亡相关因子的影响，进一步探讨松萝提取物对CIA大鼠关节炎症及高迁移率族蛋白B1（HMGB1）介导的细胞自噬的影响。方法：将54只Wistar雌性大鼠随机分为空白对照组，模型对照组，羟氯喹组，松萝提取物低、中、高剂量组，每组9只。松萝提取物低、中、高剂量组给药剂量分别为2 mg·kg^-1、6 mg·kg^-1、54 mg·kg^-1，羟氯喹组给药剂量为36 mg·kg^-1。建立CIA大鼠模型后，连续灌胃给药28 d。ELISA法检测血清中HMGB1、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）的浓度，RT-PCR检测HMGB1、Beclin1、PI3K C3 mRNA的表达，Western Blot法检测HMGB1、Beclin1、PI3K C3蛋白表达。结果：与空白对照组比较，各模型组HMGB1、TNF-α、IL-1β含量均增高，HMGB1、PI3K C3蛋白表达上升，Beclin1蛋白表达下降，差异有统计学意义（P < 0.05）；与模型对照组比较，松萝提取物中、高剂量组和羟氯喹组HMGB1、TNF-α、IL-1β含量均降低，且HMGB1、PI3K C3蛋白表达下降，Beclin1蛋白表达上升，差异有统计学意义（P < 0.05）。结论：松萝提取物通过上调Beclin1蛋白，下调HMGB1、PI3K C3相关蛋白的表达，调节细胞自噬，降低CIA大鼠血清中HMGB1、IL-1β、TNF-α浓度，减轻关节炎症。

　　【关键词】　类风湿关节炎；松萝提取物；胶原诱导性关节炎；高迁移率族蛋白B1；关节炎症；自噬；大鼠

Effects of Usnea Extract on Cell Autophagy and Inflammatory Factors Mediated by High Mobility Group Protein B1 in Collagen Induced Arthritis Rats

WEN Hong,AN Yang,ZHANG Jun,XU Hui,LU Dao-min,CAO Yue-peng,NING Qiao-yi,WANG Ying

　　【ABSTRACT】Objective:To study the effect of Usnea extract on apoptosis related factors in synovial cells of collagen induced arthritis（CIA）rats,and further explore its effect on joint inflammation and high mobility group protein B1（HMGB1）mediated cell autophagy in CIA rats.Methods:Fifty-four female Wistar rats were randomly divided into a blank control group,a model control group,a hydroxychloroquine group,and low,medium,and high dose groups of Usnea extract,with 9 rats in each group.The low,medium,and high dose groups of Usnea extract were administered with doses of 2 mg·kg^-1,6 mg·kg^-1,54 mg·kg^-1,respectively,while the hydroxychloroquine group was administered with dose of 36 mg·kg^-1.After establishing a CIA rat model,the drug was continuously administered by gavage for 28 d.ELISA method was used for detecting the concentration of HMGB1,IL-1β and TNF-α;RT-PCR was used to detect the expression of HMGB1,Beclin1 and PI3K C3 mRNA;and WB method was used to detect the the protein expression levels of HMGB1,Beclin1,and PI3K C3.Results:Compared with the blank control group,the content of HMGB1,TNF- α and IL-1β in each model group increased,the protein expression of HMGB1 and PI3K C3 increased,while the protein expression of Beclin1 decreased,with a statistically significant difference（P < 0.05）.Compared with the model control group,the content of HMGB1,TNF-α and IL-1β in the middle and high dose groups of Usnea extract and the hydroxychloroquine group decreased,the content decreased,and the protein expression of HMGB1 and PI3K C3 decreased,while the protein expression of Beclin1 increased,with a statistically significant difference（P < 0.05）.Conclusion:Usnea extract up-regulates Beclin1 protein,down-regulates the expression of HMGB1 and PI3K C3 related proteins,regulates cell autophagy,and reduces the concentration of HMGB1,IL-1β and TNF-α in serum of CIA rats,and reduces joint inflammation.

　　【Keywords】 rheumatoid arthritis;Usnea extract;collagen induced arthritis;HMGB1;joint inflammation;autophagy;rats