蒜氨酸治疗类风湿关节炎大鼠模型潜在分子机制实验研究  

Potential molecular mechanism of alliin in treatment of rheumatoid arthritis in rat model

作　　者：许良[1,2] 古丽米拉·木合塔尔 李若宁 谭永升 张裴 XU Liang;MUHETAER·Gulimila;LI Ruoning;TAN Yongsheng;ZHANG Pei(The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Institute of Medical Science,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第五附属医院,新疆乌鲁木齐830011 [2]新疆医科大学医学科学研究所,新疆乌鲁木齐830011

出　　处：《陕西医学杂志》2025年第3期307-313,共7页Shaanxi Medical Journal

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C580);新疆医科大学医学科学研究所开放课题(YXYJ20240203);新疆医科大学大学生创新训练计划项目(S202310760050)。

摘　　要：目的:探讨蒜氨酸对类风湿关节炎(RA)大鼠模型的治疗效果及其潜在机制。方法:50只健康雄性8周龄SD大鼠被随机分为对照组、模型组、阳性药物组(MTX治疗)、蒜氨酸低剂量组和蒜氨酸高剂量组。通过Ⅱ型胶原(CⅡ)和弗氏完全佐剂(CFA)诱导RA大鼠模型,并通过腹腔注射甲氨蝶呤(MTX)和蒜氨酸进行治疗。收集各组大鼠关节滑膜组织和外周血样本,HE染色评估组织炎症及病理变化,酶联免疫吸附试验(ELISA)检测炎症因子白细胞介素-6(IL-6)和氧化应激标志物[丙二醛(MDA)和活性氧(ROS)]水平,实时荧光定量PCR(RT-qPCR)和Western blot检测蒜氨酸靶标基因[表皮生长因子受体(EGFR)和犬尿氨酸酶(KYNU)]以及线粒体自噬相关蛋白[动力相关蛋白1(DRP1)、微管相关蛋白1轻链3B(LC3B)和泛素结合蛋白p62(p62)]表达,分析核因子-κB p65亚基(p65)和核因子-κB RELB亚基(RELB)信号通路激活状态。结果:模型组大鼠关节出现明显水肿和炎症,阳性药物组和蒜氨酸高剂量组显著减轻了这些症状。HE染色显示,模型组滑膜组织炎症严重,而阳性药物组和蒜氨酸高剂量组炎症明显减少。模型组IL-6、MDA和ROS表达高于对照组,阳性药物组和蒜氨酸高剂量组IL-6和MDA表达低于模型组(均P<0.05)。模型组EGFR、KYNU、DRP1、LC3B表达高于对照组,经阳性药物和高剂量蒜氨酸治疗后下降(均P<0.05);同时,模型组线粒体融合蛋白(MFN2)和p62表达低于对照组,经阳性药物和高剂量蒜氨酸治疗后上升(均P<0.05)。模型组p-p65和p-RELB表达高于对照组,经阳性药物和高剂量蒜氨酸治疗后下降(均P<0.05)。结论:蒜氨酸能够有效减轻RA大鼠模型中的炎症和氧化应激,其作用机制可能是改善线粒体自噬功能以及抑制p65和RELB信号通路的过度激活。Objective:To investigate the therapeutic effect of alliin on rheumatoid arthritis(RA)in rat model and its potential mechanism.Methods:Fifty 8-week-old male SD rats were randomly divided into control group,model group,positive drug group(MTX treatment),low-dose alliin group and high-dose alliin group.RA rat model was induced by typeⅡcollagen(CⅡ)and complete Freund’s adjuvant(CFA),and treated by intraperitoneal injection of methotrexate(MTX)and alliin.Joint synovial tissue and peripheral blood samples were collected from each group.HE staining was performed to assess tissue inflammation and pathological changes.Levels of the inflammatory cytokine IL-6 and oxidative stress markers(MDA and ROS)were measured using ELISA.RT-qPCRand Western blot were used to detect the expression of alliin target genes(EGFRand KYNU)and mitochondrial autophagy-related proteins(DRP1,LC3B and p62).The activation status of p65 and RELB signaling pathways was also analyzed.Results:The model group exhibited significant joint swelling and inflammation,which was notably alleviated in the positive drug and high-dose alliin groups.HE staining revealed severe synovial inflammation in the model group,while inflammation was significantly reduced in the positive drug and high-dose alliin groups.IL-6,MDA and ROS levels in model group were significantly higher than in control group,but IL-6 and MDA levels were markedly decreased in the positive drug and high-dose alliin groups(all P<0.05).The expressions of EGFR,KYNU,DRP1 and LC3B was significantly upregulated in model group compared to control group,but decreased significantly after treatment with positive drug and high-dose alliin(all P<0.05);meanwhile,the expression of MFN2 and p62 was lower in model group than those in control group,but significantly increased following positive drug and high-dose alliin treatment(all P<0.05).The expressions of p-p65 and p-RELB in model group were higher than those in control group,and decreased after positive drug and high-dose alliin treatment(all P<0.05).C

关 键 词：类风湿关节炎 蒜氨酸 线粒体自噬 炎症因子 氧化应激 

分 类 号：R285.5[医药卫生—中药学]