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甘草酸、桂皮酸干预类风湿关节炎的作用研究——基于MicroRNA22调控HIF-1α-MMP1/3通路 被引量:6

Effect of Glycyrrhizic Acid and Cinnamic Acid on Rheumatoid Arthritis Based on MicroRNA22 Regulating HIF-1α-MMP1/3 Pathway
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摘要 目的:研究甘草酸、桂皮酸对CIA模型大鼠MicroRNA22、HIF-1α、MMP1以及MMP3表达的影响,探讨甘草酸、桂皮酸通过MicroRNA22调控HIF-1α-MMP1/3通路干预RA的分子机理。方法:48只Wistar大鼠随机分为正常组、模型组、甘草酸组、桂皮酸组、甘草酸桂皮酸合用组、雷公藤多苷组。除正常组外,建立CIA动物模型20d,后药物干预20d。足爪大体图片、X射线影像显现骨组织变化;HE染色观察滑膜组织形态学改变;免疫组化、ELISA法检测滑膜、血清中HIF-1α、MMP1、MMP3表达变化;RT-PCR法检测脾脏中MicroRNA22表达变化。结果:造模后第20天症状最严重,大鼠双后足跖逐步红肿、畸形,更甚者表现为溶骨、成骨。给药后上述症状逐渐减轻,甘草酸桂皮酸合用组和雷公藤多苷组溶骨现象基本消失。HE染色结果提示模型组炎性细胞大量浸润,滑膜细胞结构破坏,血管显著增生;给药组炎性细胞浸润与血管新生均被抑制,甘草酸桂皮酸合用组改善作用最强。与正常组比较,模型组脾组织中MicroRNA22表达明显下调,而血清及滑膜组织中HIF-1α、MMP1、MMP3明显上调;各给药组MicroRNA22表达较之模型组均明显上调,甘草酸组、甘草酸桂皮酸合用组MicroRNA22表达还显著高于正常组,而上述蛋白表达较之模型组均明显下调。结论:甘草酸、桂皮酸治疗RA的机制可能是通过上调MicroRNA22,抑制HIF-1α-MMP1/3信号通路中相关分子生成,从而控制炎性发展,降低骨与软骨组织损伤,减少新生血管生成。 Objective:To observe the effects of glycyrrhizic acid and cinnamic acid on the expression of MicroRNA22,HIF-1α,MMP1 and MMP3 in CIA model rats,and to explore the molecular mechanism of glycyrrhizic acid and cinnamic acid regulating HIF-1α-MMP1/3 pathway through MicroRNA22 to intervene RA.Methods:48 Wistar rats were randomly divided into normal group,model group,glycyrrhizic acid group,cinnamic acid group,combined group of glycyrrhizic acid and cinnamic acid,tripterygium glycosides group.Except the normal group,CIA animal model was established for 20 days,and then drug intervention was conducted for 20 days.The gross pictures and X-ray images of feet showed the changes of bone tissue,and the morphological changes of synovium were observed by HE staining;the expression of HIF-1α,MMP1 and MMP3 in synovium and serum were detected by immunohistochemistry and ELISA;the expression of microrna22 in spleen was detected by RT-PCR.Results:On the 20 th day after modeling,the symptoms were the most serious.The hind paws of rats were gradually red,swollen and deformed,and even worse,osteolysis and osteogenesis were observed.After administration,the above symptoms gradually alleviated,and the osteolytic phenomenon disappeared in the combined group of glycyrrhizic acid and cinnamic acid and tripterygium glycosides group.The results of HE staining showed that inflammatory cell infiltration,synovial cell structure destruction and vascular proliferation were observed in model group;inflammatory cell infiltration and angiogenesis were inhibited in drug administration group,and combined group of glycyrrhizic acid and cinnamic acid had the strongest improvement effect.Compared with the normal group,the expression of MicroRNA22 in spleen tissue of model group was significantly decreased,while HIF-1α,MMP1 and MMP3 in serum and synovial tissue were significantly increased;the expression of MicroRNA22 in each treatment group was significantly higher than that in the model group,and even the expression of MicroRNA 22 in the glycyrrhizic acid group and combined group of glycyrrhizic acid and cinnamic acid was significantly higher than that in the normal group,and the above-mentioned protein expression was significantly down regulated compared with the model group.Conclusion:The mechanism of glycyrrhizic acid and cinnamic acid in the treatment of RA may be through up regulating microrna 22 and inhibiting HIF-1α-MMP1/3 signaling pathway related molecules,so as to control the development of inflammation,reduce bone and cartilage tissue damage,reduce angiogenesis.
作者 邹俊萍 王永萍 张阳 Zou Junping;Wang Yongping;Zhang Yang(Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China)
机构地区 贵州中医药大学
出处 《亚太传统医药》 2021年第3期16-22,共7页 Asia-Pacific Traditional Medicine
基金 国家自然科学基金结余经费转校内课题(2019)
关键词 甘草酸 桂皮酸 类风湿关节炎 MicroRNA22 HIF-1α-MMP1/3通路 Glycyrrhizic Acid Cinnamic Acid Rheumatoid Arthritis MicroRNA22 HIF-1α-MMP1/3 Pathway
作者简介 邹俊萍(1994-),女,贵州中医药大学硕士研究生,研究方向为炎症性疾病的分子机制;通讯作者:王永萍(1977-),女,贵州中医药大学副教授,研究方向为炎症性疾病的分子机制。E-mail:wangyongping0924@foxmail.com
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