| 林朋朝,周晓彬,高伟静,等.盘龙七片调控 Toll样受体 4-骨髓样分化因子 88-核因子 -κB通路保护佐剂性关节炎大鼠滑膜组织[J].安徽医药,2021,25(9):1713-1717. |
| 盘龙七片调控 Toll样受体 4-骨髓样分化因子 88-核因子 -κB通路保护佐剂性关节炎大鼠滑膜组织 |
| Panlongqi tablets protect synovial tissue in rats with adjuvant arthritis by regulating Toll-like receptor 4-myeloid differentiation factor 88-nuclear factor-κB pathways |
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| DOI：10.3969/j.issn.1009-6469.2021.09.004 |
| 中文关键词: 关节炎，实验性 盘龙七片 Toll样受体 4 骨髓样分化因子 88 核因子 -κB |
| 英文关键词: Arthritis, experimental Panlongqi tablets Toll-like receptor 4 Myeloid differentiation factor 88 Nuclear factor |
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| 摘要点击次数: 1377 |
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| 中文摘要: |
| 目的研究盘龙七片通过调控 Toll样受体 4(TLR4)-骨髓样分化因子 88(MyD88)-核因子 -κB(NF-κB)信号通路保护类风湿关节炎( RA)大鼠滑膜组织的作用机制。方法将 50只 SD大鼠以随机数字表法分为正常组，模型组，低、中、高盘龙七片组，每组 10只，除正常组外，其余组均采用风、寒、湿环境结合弗氏完全佐剂注射的方式制备 RA模型， RA大鼠模型制备成功后，低、中、高盘龙七片组分别灌胃给予盘龙七片溶液 150 mg/kg、300 mg/kg、600 mg/kg，对照组与模型组大鼠给予等量生理盐水灌胃，连续灌胃处理 15 d后，切片观察滑膜组织病理形态，酶联免疫吸附测定( ELISA)检测各组大鼠血清中肿瘤坏死因子 -α(TNF-α)、白细胞介素 -1(IL-1)水平，实时荧光定量逆转录聚合酶链反应( qRT-PCR)检测各组大鼠滑膜组织细胞中 TLR4 mRNA、MyD88 mRNA以及肿瘤坏死因子受体相关因子 6(TRAF-6)mRNA的表达水平，蛋白质印迹法检测滑膜组织中 NF-κB p65蛋白表达情况。结果与正常组相比，模型组滑膜组织可见明显变性坏死，滑膜处可见中度充血水肿，且有大量炎细胞并伴随轻度滑膜增生，与模型组相比，不同剂量盘龙七片处理后关节变性坏死情况明显改善，滑膜组织充血水肿情况减轻，炎细胞浸润情况极大的改善，且呈浓度依赖；模型组大鼠血清中 TNF-α、IL-1分别为( 1.26±0.11)μg/L、(0.35±0.08)μg/L，显著高于正常组的( 0.68±0.05)μg/L、(0.11±0.02)μg/L，滑膜组织中 TLR4、MyD88、TRAF-6的 mRNA相对表达水平分别为( 2.56±0.21)、(3.83±0.26)、(2.78±0.23)，显著高于正常组( 1.00±0.02)、(1.01±0.02)、(1.00±0.01)(P<0.05)NF-κB p65蛋白磷酸化水平为(1.37±0.22)显著高于正常组( 0.21±0.06)(P<0.05)，与模型组相比，不同剂量盘龙七片组大清中 TNF-α、IL-1水平显著降低( P<0.05)膜组织中 TLR4、MyD88、TRAF-6的 mRNA相对表达水平显著降低( P<0.05)，NF-κB p65蛋白磷酸化水平也显著降低( P<0.05。结论盘龙七片通过抑制 TLR4-MyD88-NF-κB信号转导通路，降低滑膜组织处炎症反应，改善滑膜细胞增生，鼠血，滑，)，从而保护滑膜组织。 |
| 英文摘要: |
| Objective To study the mechanism of Panlongqi tablets on protecting synovial tissue in rats with rheumatoid arthritis (RA) by regulating Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signaling path‐ways.Methods According to random number table method, 50 SD rats were randomly assigned into normal group, model group, low-dose, medium-dose and high-dose Panlongqi tablets groups, with 10 cases in each group. Except for normal group, the other groups were given wind-cold-wet environment and Freund's complete adjuvant injection to prepare RA models. After successful preparation of RA rat models, low-dose, medium-dose and high-dose Panlongqi tablet groups were intragastrically administered with Panlongqi tablet solutions of 150 mg/kg, 300 mg/kg and 600 mg/kg, respectively. The control group and model group were given the same amount of normal saline. After 15d of continuous intragastric administration, slice observation was performed on pathological morphology of synovialtissue. The enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of serum tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) in each group. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was applied to detect the expression levels of TLR4 mRNA, MyD88 mRNA and TNF-α receptor associated factor 6 (TRAF-6) mRNA in synovial tissue cells of each group. Western blotting was applied to detect the expression of NF-κB p65 protein in synovial tissue.Results Compared withnormal group, there was significant degenerative necrosis of synovial tissue in model group. Moderate congestive edema could be foundat synovium site, and there was a large number of inflammatory cells, accompanied with mild synovial hyperplasia. Compared with model group, after treatment with different doses of Panlongqi tablets, degenerative necrosis of joints was significantly improved, congestiveedema of synovial tissue was alleviated, and inflammatory cells infiltration was greatly improved, showing concentration-dependence. The levels of serum TNF-α and IL-1 in model group rats were (1.26±0.11) μg/L and (0.35±0.08) μg/L, significantly higher than thosein normal group [(0.68±0.05) μg/L, (0.11±0.02) μg/L], relative expression levels of TLR4, MyD88 and TRAF-6 mRNA in synovial tissue were (2.56±0.21), (3.83±0.26) and (2.78±0.23), significantly higher than those in normal group [(1.00 ±0.02), (1.01±0.02), (1.00±0.01), respectively] (P<0.05), and phosphorylation level of NF-κB p65 protein was significantly higher than that in normal group [(1.37± 0.22) vs. (0.21±0.06), P<0.05]. Compared with model group, levels of serum TNF-α and IL-1 were significantly decreased in groups with different doses of Panlongqi tablets (P<0.05), relative expression levels of TLR4, MyD88 and TRAF-6 mRNA in synovial tissue were significantly decreased (P<0.05), and phosphorylation level of NF-κB p65 protein was also significantly decreased (P<0.05).Con? clusion Panlongqi tablets decrease inflammation reaction in synovial tissue and improve synovial cell hyperplasia by inhibiting TLR4-MyD88-NF-κB signal transduction pathways, thereby protecting synovial tissue. |
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