首页|松萝酸对类风湿关节炎成纤维样滑膜细胞HMGB1/RAGE炎症通路及VEGF、IL-6、IL-1β表达的影响

松萝酸对类风湿关节炎成纤维样滑膜细胞HMGB1/RAGE炎症通路及VEGF、IL-6、IL-1β表达的影响

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目的 构建类风湿关节炎(RA)成纤维样滑膜细胞(RAFLS)模型,研究松萝酸对其高迁移率族蛋白B1(HMGB1)/晚期糖基化终产物受体(RAGE)炎症通路及血管内皮生长因子(VEGF)、白细胞介素(IL)-6、IL-1β表达的影响。方法 选取贵州中医药大学第二附属医院骨科行关节置换治疗的RA患者,于术中获取滑膜组织。将细胞分为空白对照组(胎牛血清)、溶剂对照组(胎牛血清+10%羟丙基倍他环糊精)、松萝酸高剂量组(松萝酸50 μg/mL)、松萝酸中剂量组(松萝酸10 μg/mL)、松萝酸低剂量组(松萝酸2。5 μg/mL)和羟氯喹组(羟氯查50 mmol/L)。MTT检测不同浓度松萝酸处理后细胞增殖情况,Western blot检测各组细胞HMGB1、RAGE蛋白表达,ELISA检测各组细胞HMGB1、VEGF、IL-6、IL-1β表达。结果 与空白对照组比较,松萝酸高、中、低剂量组及羟氯喹组细胞凋亡比例增加(P<0。05),松萝酸高、中剂量组和羟氯喹组HMGB1、RAGE蛋白表达明显降低(P<0。05),松萝酸高、中、低剂量组和羟氯喹组HMGB1、VEGF、IL-6、IL-1β表达均降低(P<0。05);与羟氯喹组比较,松萝酸中、低剂量组细胞凋亡比例减少(P<0。05),松萝酸低剂量组HMGB1蛋白表达明显升高(P<0。05),松萝酸中、低剂量组RAGE蛋白表达明显升高(P<0。05)。结论 松萝酸可能通过调控HMGB1/RAGE炎症通路及VEGF、IL-6、IL-1β等炎症因子表达,减轻滑膜细胞的炎症反应。
Effect of usnic acid on HMGB1/RAGE inflammatory pathway in fibroblast-like synoviocytes of RA and VEGF,IL-6 and IL-1β expression levels
Objective To construct the rheumatoid arthritis fibroblast-like synoviocytes(RAFLS)model,and to investigate the effects of usnic acid on the inflammatory pathway of high-mobility group protein B1(HMGB1)/receptor for activated glycation end products(RAGE)and the expression levels of vascular en-dothelial growth factor(VEGF),interleukin(IL)-6 and IL-1β.Methods The patients with RA undergoing joint replacement surgery in the orthopedic department of the Second Affiliated Hospital of Guizhou Universi-ty of Traditional Chinese Medicine were selected and the synovial tissues were obtained during operation.The cells were divided into the blank control group(fetal calf serum),solvent control group(fetal calf serum+10%hydroxypropyl betacyclodextrin),usnic acid high dose group(usnic acid 50 μg/mL),usnic acid middle dose group(usnic acid 10 μg/mL),usnic acid low dose group(usnic acid 2.5 μg/mL)and hydroxychloroquine group(hydroxychloroquine 50 mmol/L).The cell proliferation after different concentrations of usnic acid treatment was detected by MTT,the HMGB1 and RAGE protein expression in cells of each group was detec-ted by Western blot,and the expression levels of HMGB1,VEGF,IL-6 and IL-1β were detected by ELISA.Re-sults Compared with the blank control group,the proportions of cellular apoptosis in the usnic acid high,middle and low doses groups and hydroxychloroquine group were increased(P<0.05);the expression levels of HMGB1 and RAGE protein in the usnic acid high,middle and low doses groups and hydroxychloroquine group were significantly decreased(P<0.05),the expression levels of HMGB1,VEGF,IL-6 and IL-1β were decreased(P<0.05);compared with the hydroxychloroquine group,the cellular apoptosis proportions of the usnic acid high,middle and low doses groups were decreased(P<0.05),the HMGB1 protein expression level in the usnic acid low dose group was significantly increased(P<005),the RAGE protein expression level in the the usnic acid middle amd low doses groups was significantly increased(P<0.05).Conclusion Usnic acid alleviates the inflammatory reaction of synoviocytes possibly by regulating HMGB1/RAGE inflammatory pathway and VEGF,IL-6 and IL-1β inflammatory factors expression levels.

rheumatoid arthritisusnic acidhigh mobility group box-1 proteinthe receptor of ad-vanced glycation end products

蔡国昌、安阳、张军、徐晖、陆道敏、宁乔怡

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贵州中医药大学,贵阳 550025

贵州中医药大学第二附属医院风湿免疫科,贵阳 550002

类风湿关节炎 松萝酸 高迁移率族蛋白B1 晚期糖基化终产物受体

国家自然科学基金项目贵州省科学技术厅项目

81960909黔科合平台人才[2020]2202号

2024

重庆医学
重庆市卫生信息中心,重庆市医学会

重庆医学

CSTPCD
影响因子:1.797
ISSN:1671-8348
年,卷(期):2024.53(19)
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