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野蔷薇根总黄酮对类风湿关节炎模型大鼠血管损伤的改善作用及机制
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| 篇名： | 野蔷薇根总黄酮对类风湿关节炎模型大鼠血管损伤的改善作用及机制 |
| TITLE： | Improvement effect and mechanism of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis model rats |
| 摘要： | 目的 研究野蔷薇根总黄酮对类风湿关节炎（RA）模型大鼠血管损伤的改善作用及其潜在机制。方法将雌性Wistar大鼠随机分为正常对照组、模型组、阿司匹林组（阳性对照，30mg/kg）和野蔷薇根总黄酮低、高剂量组（4.15、8.30g/kg，以生药量计），每组10只。除正常对照组外，其余各组大鼠采用胶原诱导+高脂饮食喂养建立RA模型。造模14d后，各组大鼠灌胃相应药液/0.5%羧甲基纤维素钠溶液，每天1次，连续36d。定期评估大鼠的全身评分、关节炎指数和足爪肿胀数；末次给药后，检测大鼠血清中白细胞介素6（IL-6）、细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）水平，观察大鼠胸主动脉血管组织病理学形态变化，检测胸主动脉血管组织中Toll样受体4（TLR4）蛋白表达水平和Janus激酶2（JAK2）、信号转导及转录激活因子3（STAT3）蛋白磷酸化水平。结果与正常对照组比较，模型组大鼠血清中IL-6、ICAM-1、VCAM-1水平和胸主动脉血管组织中TLR4蛋白表达水平及JAK2、STAT3蛋白磷酸化水平均显著升高（P＜0.01），胸主动脉血管组织可见动脉粥样斑块（粥瘤）、胆固醇结晶、淋巴细胞浸润及少量未破裂的泡沫细胞聚集。与模型组比较，在第28天时，野蔷薇根总黄酮各剂量组大鼠的全身评分（低剂量组除外）、关节炎指数和足爪肿胀数均显著降低（P＜0.05或P＜0.01）；在第49天时，野蔷薇根总黄酮低剂量组大鼠的全身评分、关节炎指数和足爪肿胀数均显著降低（P＜0.05或P＜0.01）；野蔷薇根总黄酮各剂量组大鼠血清和血管组织中其余定量指标均显著逆转（P＜0.05或P＜0.01），血管组织病理损伤明显减轻。结论野蔷薇根总黄酮可改善RA模型大鼠的血管损伤，其作用可能与降低血管组织中TLR4蛋白表达，抑制IL-6/JAK2/STAT3信号通路活性有关。 |
| ABSTRACT： | OBJECTIVE To study the improvement effect of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis （RA） model rats and its potential mechanism. METHODS Female Wistar rats were randomly divided into normal control group， model group， aspirin group （positive control， 30 mg/kg）， low-dose and high-dose groups of total flavonoids from R. multiflora root （4.15， 8.30 g/kg， by crude drug）， with 10 rats in each group. Except for the normal control group， the RA model was induced in other groups by collagen induction and high-fat diet. After 14 days of modeling， they were given corresponding drug solution/0.5% sodium carboxymethyl cellulose solution intragastrically， once a day， for 36 consecutive days. The total body score， arthritis index （AI） and swollen joint count （SJC） of the rats were evaluated regularly. After the last medication， serum levels of interleukin-6 （IL-6）， intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule- 1 （VCAM-1） were determined. The pathological morphological changes in the vascular tissue of thoracic aorta were observed； the protein expression of Toll-like receptor 4 （TLR4） and the protein phosphorylation levels of Janus kinase 2 （JAK2） and signal transduction and activator of transcription 3 （STAT3） in vascular tissue of thoracic aorta were measured. RESULTS Compared with the normal control group， serum levels of IL-6， ICAM-1 and VCAM-1， protein expression of TLR4， and the protein phosphorylation levels of JAK2 and STAT3 in vascular tissue of thoracic aorta were increased significantly in model group （P＜ 0.01）. The atherosclerotic plaque （atheroma）， cholesterol crystal， lymphocyte infiltration and a small number of unbroken foam cell aggregation could be seen in the vascular tissue of thoracic aorta. Compared with the model group， total body score （except for the low-dose group）， AI and SJC were decreased significantly in groups of total flavonoids from R. multiflora root on the 28th day （P＜0.05 or P＜0.01）； total body score，AI and SJC were decreased significantly in low-dose group of total flavonoids from R. multiflora root on the 49th day （P＜0.05 or P＜0.01）； the other quantitative indicators in serum and vascular tissue were significantly reversed in groups of total flavonoids from R. multiflora root （P＜0.05 or P＜0.01）， and pathological damage of vascular tissue was significantly relieved. CONCLUSIONS Total flavonoids from R. multiflora root can significantly improve vascular injury in RA model rats， and its mechanism may be related to reducing the protein expression of TLR4 in vascular tissue and inhibiting the activation of IL-6/JAK2/ STAT3 signaling pathway. |
| 期刊： | 2024年第35卷第08期 |
| 作者： | 李开言；张飞；田萍；杨丹；张薇；王晓丽；屠万倩；刘一菲 |
| AUTHORS： | LI Kaiyan，ZHANG Fei，TIAN Ping，YANG Dan，ZHANG Wei，WANG Xiaoli，TU Wanqian，LIU Yifei |
| 关键字： | 野蔷薇根总黄酮；类风湿关节炎；炎症；血管损伤；TLR4；IL-6/JAK2/STAT3信号通路 |
| KEYWORDS： | total flavonoids from Rosa multiflora root； rheumatoid arthritis； inflammation； vascular injury； TLR4； IL-6/JAK2/ |
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